Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.
A class of drugs that act by selective inhibition of calcium influx through cellular membranes.
Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.
Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.
CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.
A heterogenous group of transient or low voltage activated type CALCIUM CHANNELS. They are found in cardiac myocyte membranes, the sinoatrial node, Purkinje cells of the heart and the central nervous system.
Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.
Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.
The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.
Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.
CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.
CALCIUM CHANNELS located in the neurons of the brain.
Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.
CALCIUM CHANNELS located in the neurons of the brain. They are inhibited by the marine snail toxin, omega conotoxin MVIIC.
A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.
A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.
Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.
A neurotoxic peptide, which is a cleavage product (VIa) of the omega-Conotoxin precursor protein contained in venom from the marine snail, CONUS geographus. It is an antagonist of CALCIUM CHANNELS, N-TYPE.
The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
Calcium compounds used as food supplements or in food to supply the body with calcium. Dietary calcium is needed during growth for bone development and for maintenance of skeletal integrity later in life to prevent osteoporosis.
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
A family of structurally related neurotoxic peptides from mollusk venom that inhibit voltage-activated entry of calcium into the presynaptic membrane. They selectively inhibit N-, P-, and Q-type calcium channels.
Potassium channel whose permeability to ions is extremely sensitive to the transmembrane potential difference. The opening of these channels is induced by the membrane depolarization of the ACTION POTENTIAL.
A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.
Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A calcium channel blocker that is a class IV anti-arrhythmia agent.
A potent antagonist of CALCIUM CHANNELS that is highly selective for VASCULAR SMOOTH MUSCLE. It is effective in the treatment of chronic stable angina pectoris, hypertension, and congestive cardiac failure.
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.
Potassium channels whose activation is dependent on intracellular calcium concentrations.
A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive.
A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE.
The ability of a substrate to allow the passage of ELECTRONS.
A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.
An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous.
A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.
A neuropeptide toxin from the venom of the funnel web spider, Agelenopsis aperta. It inhibits CALCIUM CHANNELS, P-TYPE by altering the voltage-dependent gating so that very large depolarizations are needed for channel opening. It also inhibits CALCIUM CHANNELS, Q-TYPE.
A subgroup of TRP cation channels that contain 3-4 ANKYRIN REPEAT DOMAINS and a conserved C-terminal domain. Members are highly expressed in the CENTRAL NERVOUS SYSTEM. Selectivity for calcium over sodium ranges from 0.5 to 10.
Voltage-gated potassium channels whose primary subunits contain six transmembrane segments and form tetramers to create a pore with a voltage sensor. They are related to their founding member, shaker protein, Drosophila.
The rate dynamics in chemical or physical systems.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A major class of calcium activated potassium channels whose members are voltage-dependent. MaxiK channels are activated by either membrane depolarization or an increase in intracellular Ca(2+). They are key regulators of calcium and electrical signaling in a variety of tissues.
An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement.
A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore-loop cation channels. They are expressed in OLFACTORY NERVE cilia and in PHOTORECEPTOR CELLS and some PLANTS.
Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A subgroup of TRP cation channels named after vanilloid receptor. They are very sensitive to TEMPERATURE and hot spicy food and CAPSAICIN. They have the TRP domain and ANKYRIN repeats. Selectivity for CALCIUM over SODIUM ranges from 3 to 100 fold.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents.
The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.
A subgroup of TRP cation channels named after melastatin protein. They have the TRP domain but lack ANKYRIN repeats. Enzyme domains in the C-terminus leads to them being called chanzymes.
A family of proton-gated sodium channels that are primarily expressed in neuronal tissue. They are AMILORIDE-sensitive and are implicated in the signaling of a variety of neurological stimuli, most notably that of pain in response to acidic conditions.
Venoms of arthropods of the order Araneida of the ARACHNIDA. The venoms usually contain several protein fractions, including ENZYMES, hemolytic, neurolytic, and other TOXINS, BIOLOGICAL.
Calcium salts of phosphoric acid. These compounds are frequently used as calcium supplements.
Established cell cultures that have the potential to propagate indefinitely.
Sodium channels found on salt-reabsorbing EPITHELIAL CELLS that line the distal NEPHRON; the distal COLON; SALIVARY DUCTS; SWEAT GLANDS; and the LUNG. They are AMILORIDE-sensitive and play a critical role in the control of sodium balance, BLOOD VOLUME, and BLOOD PRESSURE.
A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.
A family of voltage-gated potassium channels that are characterized by long N-terminal and C-terminal intracellular tails. They are named from the Drosophila protein whose mutation causes abnormal leg shaking under ether anesthesia. Their activation kinetics are dependent on extracellular MAGNESIUM and PROTON concentration.
Stable calcium atoms that have the same atomic number as the element calcium, but differ in atomic weight. Ca-42-44, 46, and 48 are stable calcium isotopes.
A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.
A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.
Unstable isotopes of calcium that decay or disintegrate emitting radiation. Ca atoms with atomic weights 39, 41, 45, 47, 49, and 50 are radioactive calcium isotopes.
Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.
A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of ANGINA PECTORIS and HYPERTENSION.
A delayed rectifier subtype of shaker potassium channels that conducts a delayed rectifier current. It contributes to ACTION POTENTIAL repolarization of MYOCYTES in HEART ATRIA.
A class of polyamine and peptide toxins which are isolated from the venom of spiders such as Agelenopsis aperta.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.
A major class of calcium-activated potassium channels that are found primarily in excitable CELLS. They play important roles in the transmission of ACTION POTENTIALS and generate a long-lasting hyperpolarization known as the slow afterhyperpolarization.
A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.
Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
The movement of ions across energy-transducing cell membranes. Transport can be active, passive or facilitated. Ions may travel by themselves (uniport), or as a group of two or more ions in the same (symport) or opposite (antiport) directions.
Elements of limited time intervals, contributing to particular results or situations.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
Venoms from mollusks, including CONUS and OCTOPUS species. The venoms contain proteins, enzymes, choline derivatives, slow-reacting substances, and several characterized polypeptide toxins that affect the nervous system. Mollusk venoms include cephalotoxin, venerupin, maculotoxin, surugatoxin, conotoxins, and murexine.
A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN repeats are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES.
A family of delayed rectifier voltage-gated potassium channels that share homology with their founding member, KCNQ1 PROTEIN. KCNQ potassium channels have been implicated in a variety of diseases including LONG QT SYNDROME; DEAFNESS; and EPILEPSY.
A subfamily of shaker potassium channels that shares homology with its founding member, Shab protein, Drosophila. They regulate delayed rectifier currents in the NERVOUS SYSTEM of DROSOPHILA and in the SKELETAL MUSCLE and HEART of VERTEBRATES.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A voltage-gated potassium channel that is expressed primarily in the HEART.
A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.
Use of electric potential or currents to elicit biological responses.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.
A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.
An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS.
Coronary vasodilator that is an analog of iproveratril (VERAPAMIL) with one more methoxy group on the benzene ring.
A family of inwardly-rectifying potassium channels that are activated by PERTUSSIS TOXIN sensitive G-PROTEIN-COUPLED RECEPTORS. GIRK potassium channels are primarily activated by the complex of GTP-BINDING PROTEIN BETA SUBUNITS and GTP-BINDING PROTEIN GAMMA SUBUNITS.
The calcium salt of gluconic acid. The compound has a variety of uses, including its use as a calcium replenisher in hypocalcemic states.
A shaker subfamily of potassium channels that participate in transient outward potassium currents by activating at subthreshold MEMBRANE POTENTIALS, inactivating rapidly, and recovering from inactivation quickly.
The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included.
A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
A fluorescent calcium chelating agent which is used to study intracellular calcium in tissues.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
A sesquiterpene lactone found in roots of THAPSIA. It inhibits CA(2+)-TRANSPORTING ATPASE mediated uptake of CALCIUM into SARCOPLASMIC RETICULUM.
The hollow, muscular organ that maintains the circulation of the blood.
A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A subgroup of cyclic nucleotide-regulated ION CHANNELS of the superfamily of pore-loop cation channels that are opened by hyperpolarization rather than depolarization. The ion conducting pore passes SODIUM, CALCIUM, and POTASSIUM cations with a preference for potassium.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
The nonstriated involuntary muscle tissue of blood vessels.
A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)
A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme UREASE.
Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.
The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.
An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Lanthanum. The prototypical element in the rare earth family of metals. It has the atomic symbol La, atomic number 57, and atomic weight 138.91. Lanthanide ion is used in experimental biology as a calcium antagonist; lanthanum oxide improves the optical properties of glass.
An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to CADMIUM POISONING.
Venoms from animals of the order Scorpionida of the class Arachnida. They contain neuro- and hemotoxins, enzymes, and various other factors that may release acetylcholine and catecholamines from nerve endings. Of the several protein toxins that have been characterized, most are immunogenic.
Contractile tissue that produces movement in animals.
A dihydropyridine calcium channel antagonist that acts as a potent arterial vasodilator and antihypertensive agent. It is also effective in patients with cardiac failure and angina.
A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of CARDIOMYOCYTES. Defects in the SCN5A gene, which codes for the alpha subunit of this sodium channel, are associated with a variety of CARDIAC DISEASES that result from loss of sodium channel function.
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A major class of calcium-activated potassium channels that were originally discovered in ERYTHROCYTES. They are found primarily in non-excitable CELLS and set up electrical gradients for PASSIVE ION TRANSPORT.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.
A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is closely related to KCNQ2 POTASSIUM CHANNEL. It is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.
The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.
An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as CATIONS; those with a negative charge are ANIONS.
Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain.
The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.
Intracellular receptors that bind to INOSITOL 1,4,5-TRISPHOSPHATE and play an important role in its intracellular signaling. Inositol 1,4,5-trisphosphate receptors are calcium channels that release CALCIUM in response to increased levels of inositol 1,4,5-trisphosphate in the CYTOPLASM.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.
A methylpyrrole-carboxylate from RYANIA that disrupts the RYANODINE RECEPTOR CALCIUM RELEASE CHANNEL to modify CALCIUM release from SARCOPLASMIC RETICULUM resulting in alteration of MUSCLE CONTRACTION. It was previously used in INSECTICIDES. It is used experimentally in conjunction with THAPSIGARGIN and other inhibitors of CALCIUM ATPASE uptake of calcium into SARCOPLASMIC RETICULUM.
A group of slow opening and closing voltage-gated potassium channels. Because of their delayed activation kinetics they play an important role in controlling ACTION POTENTIAL duration.
A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A voltage-gated sodium channel subtype that mediates the sodium ion permeability of excitable membranes. Defects in the SCN2A gene which codes for the alpha subunit of this sodium channel are associated with benign familial infantile seizures type 3, and early infantile epileptic encephalopathy type 11.
A family of membrane proteins that selectively conduct SODIUM ions due to changes in the TRANSMEMBRANE POTENTIAL DIFFERENCE. They typically have a multimeric structure with a core alpha subunit that defines the sodium channel subtype and several beta subunits that modulate sodium channel activity.
Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.
Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).
A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.
A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.
Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.
The physical characteristics and processes of biological systems.
Proteins prepared by recombinant DNA technology.
The fluid inside CELLS.
Refers to animals in the period of time just after birth.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
An element of the alkaline earth family of metals. It has the atomic symbol Sr, atomic number 38, and atomic weight 87.62.
Flunarizine is a selective calcium entry blocker with calmodulin binding properties and histamine H1 blocking activity. It is effective in the prophylaxis of migraine, occlusive peripheral vascular disease, vertigo of central and peripheral origin, and as an adjuvant in the therapy of epilepsy.
An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.
Inorganic compounds that contain calcium as an integral part of the molecule.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.
One of the POTASSIUM CHANNEL BLOCKERS, with secondary effect on calcium currents, which is used mainly as a research tool and to characterize channel subtypes.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.
Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis.
A highly neurotoxic polypeptide from the venom of the honey bee (Apis mellifera). It consists of 18 amino acids with two disulfide bridges and causes hyperexcitability resulting in convulsions and respiratory paralysis.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.
A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.
A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.
Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
ATP-BINDING CASSETTE PROTEINS that are highly conserved and widely expressed in nature. They form an integral part of the ATP-sensitive potassium channel complex which has two intracellular nucleotide folds that bind to sulfonylureas and their analogs.
Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)
The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
The excitable plasma membrane of a muscle cell. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of SKELETAL MYOCYTES. Defects in the SCN4A gene, which codes for the alpha subunit of this sodium channel, are associated with several MYOTONIC DISORDERS.
A family of voltage-gated eukaryotic porins that form aqueous channels. They play an essential role in mitochondrial CELL MEMBRANE PERMEABILITY, are often regulated by BCL-2 PROTO-ONCOGENE PROTEINS, and have been implicated in APOPTOSIS.
The processes whereby the internal environment of an organism tends to remain balanced and stable.
Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall.
The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)
A proline analog that acts as a stoichiometric replacement of proline. It causes the production of abnormal proteins with impaired biological activity.
Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.
One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.
The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.

Functional consequences of mutations in the human alpha1A calcium channel subunit linked to familial hemiplegic migraine. (1/613)

Mutations in alpha1A, the pore-forming subunit of P/Q-type calcium channels, are linked to several human diseases, including familial hemiplegic migraine (FHM). We introduced the four missense mutations linked to FHM into human alpha1A-2 subunits and investigated their functional consequences after expression in human embryonic kidney 293 cells. By combining single-channel and whole-cell patch-clamp recordings, we show that all four mutations affect both the biophysical properties and the density of functional channels. Mutation R192Q in the S4 segment of domain I increased the density of functional P/Q-type channels and their open probability. Mutation T666M in the pore loop of domain II decreased both the density of functional channels and their unitary conductance (from 20 to 11 pS). Mutations V714A and I1815L in the S6 segments of domains II and IV shifted the voltage range of activation toward more negative voltages, increased both the open probability and the rate of recovery from inactivation, and decreased the density of functional channels. Mutation V714A decreased the single-channel conductance to 16 pS. Strikingly, the reduction in single-channel conductance induced by mutations T666M and V714A was not observed in some patches or periods of activity, suggesting that the abnormal channel may switch on and off, perhaps depending on some unknown factor. Our data show that the FHM mutations can lead to both gain- and loss-of-function of human P/Q-type calcium channels.  (+info)

Activation of human D3 dopamine receptor inhibits P/Q-type calcium channels and secretory activity in AtT-20 cells. (2/613)

The D3 dopamine receptor is postulated to play an important role in the regulation of neurotransmitter secretion at both pre- and postsynaptic terminals. However, this hypothesis and the underlying mechanisms remain untested because of the lack of D3-selective ligands, paucity of appropriate model secretory systems, and the weak and inconsistent coupling of D3 receptors to classical signal transduction pathways. The absence of ligands that selectively discriminate between D3 and D2 receptors in vivo precludes the study of D3 receptor function in the brain and necessitates the use of heterologous expression systems. In this report we demonstrate that activation of the human D3 dopamine receptor expressed in the AtT-20 neuroendocrine cell line causes robust inhibition of P/Q-type calcium channels via pertussis toxin-sensitive G-proteins. In addition, using the vesicle trafficking dye FM1-43, we show that D3 receptor activation significantly inhibits spontaneous secretory activity in these cells. Our results not only support the hypothesis that the D3 receptor can regulate secretory activity but also provide insight into the underlying signaling mechanisms. We propose a functional model in which the D3 receptor tightly regulates neurotransmitter release at a synapse by only allowing the propagation of spikes above a certain frequency or burst-duration threshold.  (+info)

Differential plasma membrane targeting of voltage-dependent calcium channel subunits expressed in a polarized epithelial cell line. (3/613)

1. Voltage-dependent calcium channels (VDCCs) show a highly non-uniform distribution in many cell types, including neurons and other polarized secretory cells. We have examined whether this can be mimicked in a polarized epithelial cell line (Madin-Darby canine kidney), which has been used extensively to study the targeting of proteins. 2. We expressed the VDCC alpha1A, alpha1B or alpha1C subunits either alone or in combination with accessory subunits alpha2-delta and the different beta subunits, and examined their localization immunocytochemically. An alpha1 subunit was only targeted to the plasma membrane if co-expressed with the accessory subunits. 3. The combination alpha1C/alpha2-delta and all beta subunits was always localized predominantly to the basolateral membrane. It has been suggested that this is equivalent to somatodendritic targeting in neurons. 4. In contrast, the alpha1B subunit was expressed at the apical membrane with all the accessory subunit combinations, by 24 h after microinjection. This membrane destination shows some parallels with axonal targeting in neurons. 5. The alpha1A subunit was consistently observed at the apical membrane in the combinations alpha1A/alpha2-delta/beta1b or beta4. In contrast, when co-expressed with alpha2-delta/beta2a, alpha1A was clearly targeted to the basolateral membrane. 6. In conclusion, the VDCC alpha1 subunit appears to be the primary determinant for targeting the VDCC complex, but the beta subunit can modify this destination, particularly for alpha1A.  (+info)

Cross-coupling between voltage-dependent Ca2+ channels and ryanodine receptors in developing ascidian muscle blastomeres. (4/613)

1. Ascidian blastomeres of muscle lineage express voltage-dependent calcium channels (VDCCs) despite isolation and cleavage arrest. Taking advantage of these large developing cells, developmental changes in functional relations between VDCC currents and intracellular Ca2+ stores were studied. 2. Inactivation of ascidian VDCCs is Ca2+ dependent, as demonstrated by two pieces of evidence: (1) a bell-shaped relationship between prepulse voltage and amplitude during the test pulse in Ca2+, but not in Ba2+, and (2) the decay kinetics of Ca2+ currents (ICa) obtained as the size of tail currents. 3. During replacement in the external solution of Ca2+ with Ba2+, the inward current appeared biphasic: it showed rapid decay followed by recovery and slow decay. This current profile was most evident in the mixed bath solution (2 % Ca2+ and 98 % Ba2+, abbreviated to '2Ca/98Ba'). 4. The biphasic profile of I2Ca/98Ba was significantly attenuated in caffeine and in ryanodine, indicating that Ca2+ release is involved in shaping the current kinetics of VDCCs. After washing out the caffeine, the biphasic pattern was reproducibly restored by depolarizing the membrane in calcium-rich solution, which is expected to refill the internal Ca2+ stores. 5. The inhibitors of endoplasmic reticulum (ER) Ca2+-ATPase (SERCAs) cyclopiazonic acid (CPA) and thapsigargin facilitated elimination of the biphasic profile with repetitive depolarization. 6. At a stage earlier than 36 h after fertilization, the biphasic profile of I2Ca/98Ba was not observed. However, caffeine induced a remarkable decrease in the amplitude of I2Ca/98Ba and this suppression was blocked by microinjection of the Ca2+ chelator BAPTA, showing the presence of caffeine-sensitive Ca2+ stores at this stage. 7. Electron microscopic observation shows that sarcoplasmic membranes (SR) arrange closer to the sarcolemma with maturation, suggesting that the formation of the ultrastructural machinery underlies development of the cross-coupling between VDCCs and Ca2+ stores.  (+info)

Voltage inactivation of Ca2+ entry and secretion associated with N- and P/Q-type but not L-type Ca2+ channels of bovine chromaffin cells. (5/613)

1. In this study we pose the question of why the bovine adrenal medullary chromaffin cell needs various subtypes (L, N, P, Q) of the neuronal high-voltage activated Ca2+ channels to control a given physiological function, i.e. the exocytotic release of catecholamines. One plausible hypothesis is that Ca2+ channel subtypes undergo different patterns of inactivation during cell depolarization. 2. The net Ca2+ uptake (measured using 45Ca2+) into hyperpolarized cells (bathed in a nominally Ca2+-free solution containing 1.2 mM K+) after application of a Ca2+ pulse (5 s exposure to 100 mM K+ and 2 mM Ca2+), amounted to 0.65 +/- 0.02 fmol cell-1; in depolarized cells (bathed in nominally Ca2+-free solution containing 100 mM K+) the net Ca2+ uptake was 0.16 +/- 0.01 fmol cell-1. 3. This was paralleled by a dramatic reduction of the increase in the cytosolic Ca2+ concentration, [Ca2+]i, caused by Ca2+ pulses applied to fura-2-loaded single cells, from 1181 +/- 104 nM in hyperpolarized cells to 115 +/- 9 nM in depolarized cells. 4. A similar decrease was observed when studying catecholamine release. Secretion was decreased when K+ concentration was increased from 1.2 to 100 mM; the Ca2+ pulse caused, when comparing the extreme conditions, the secretion of 807 +/- 35 nA of catecholamines in hyperpolarized cells and 220 +/- 19 nA in depolarized cells. 5. The inactivation by depolarization of Ca2+ entry and secretion occluded the blocking effects of combined omega-conotoxin GVIA (1 microM) and omega-agatoxin IVA (2 microM), thus suggesting that depolarization caused a selective inactivation of the N- and P/Q-type Ca2+ channels. 6. This was strengthened by two additional findings: (i) nifedipine (3 microM), an L-type Ca2+ channel blocker, suppressed the fraction of Ca2+ entry (24 %) and secretion (27 %) left unblocked by depolarization; (ii) FPL64176 (3 microM), an L-type Ca2+ channel 'activator', dramatically enhanced the entry of Ca2+ and the secretory response in depolarized cells. 7. In voltage-clamped cells, switching the holding potential from -80 to -40 mV promoted the loss of 80 % of the whole-cell inward Ca2+ channel current carried by 10 mM Ba2+ (IBa). The residual current was blocked by 80 % upon addition of 3 microM nifedipine and dramatically enhanced by 3 microM FPL64176. 8. Thus, it seems that the N- and P/Q-subtypes of calcium channels are more prone to inactivation at depolarizing voltages than the L-subtype. We propose that this different inactivation might occur physiologically during different patterns of action potential firing, triggered by endogenously released acetylcholine under various stressful conditions.  (+info)

Calmodulin is the Ca2+ sensor for Ca2+ -dependent inactivation of L-type calcium channels. (6/613)

Elevated intracellular Ca2+ triggers inactivation of L-type calcium channels, providing negative Ca2+ feedback in many cells. Ca2+ binding to the main alpha1c channel subunit has been widely proposed to initiate such Ca2+ -dependent inactivation. Here, we find that overexpression of mutant, Ca2+ -insensitive calmodulin (CaM) ablates Ca2+ -dependent inactivation in a "dominant-negative" manner. This result demonstrates that CaM is the actual Ca2+ sensor for inactivation and suggests that CaM is constitutively tethered to the channel complex. Inactivation is likely to occur via Ca2+ -dependent interaction of tethered CaM with an IQ-like motif on the carboxyl tail of alpha1c. CaM also binds to analogous IQ regions of N-, P/Q-, and R-type calcium channels, suggesting that CaM-mediated effects may be widespread in the calcium channel family.  (+info)

Calcium channels involved in synaptic transmission from reticulospinal axons in lamprey. (7/613)

The pharmacology of calcium channels involved in glutamatergic synaptic transmission from reticulospinal axons in the lamprey spinal cord was analyzed with specific agonists and antagonists of different high-voltage activated calcium channels. The N-type calcium channel blocker omega-conotoxin GVIA (omega-CgTx) induced a large decrease of the amplitude of reticulospinal-evoked excitatory postsynaptic potentials (EPSPs). The P/Q-type calcium channel blocker omega-agatoxin IVA (omega-Aga) also reduced the amplitude of the reticulospinal EPSPs, but to a lesser extent than omega-CgTx. The dihydropyridine agonist Bay K and antagonist nimodipine had no effect on the amplitude of the reticulospinal EPSP. Combined application of omega-CgTx and omega-Aga strongly decreased the amplitude the EPSPs but was never able to completely block them, indicating that calcium channels insensitive to these toxins (R-type) are also involved in synaptic transmission from reticulospinal axons. We have previously shown that the group III metabotropic glutamate receptor agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) mediates presynaptic inhibition at the reticulospinal synapse. To test if this presynaptic effect is mediated through inhibition of calcium influx, the effect of L-AP4 on reticulospinal transmission was tested before and after blockade of N-type channels, which contribute predominantly to transmitter release at this synapse. Blocking the N-type channels with omega-CgTx did not prevent inhibition of reticulospinal synaptic transmission by L-AP4. In addition, L-AP4 had no affect on the calcium current recorded in the somata of reticulospinal neurons or on the calcium component of action potentials in reticulospinal axons. These results show that synaptic transmission from reticulospinal axons in the lamprey is mediated by calcium influx through N-, P/Q- and R-type channels, with N-type channels playing the major role. Furthermore, presynaptic inhibition of reticulospinal transmission by L-AP4 appears not to be mediated through inhibition of presynaptic calcium channels.  (+info)

Inositol 1,3,4,5-tetrakisphosphate enhances long-term potentiation by regulating Ca2+ entry in rat hippocampus. (8/613)

1. The effect of inositol 1,3,4,5-tetrakisphosphate (InsP4) on long-term potentiation (LTP) was investigated in the CA1 region of rat hippocampal slices. Intracellular application of InsP4 and EPSP recordings were carried out using the whole-cell configuration. 2. Induction of LTP in the presence of InsP4 (100 microM) resulted in a substantial enhancement of the LTP magnitude compared with control potentiation. Using an intrapipette perfusion system, it was established that application of InsP4 was required during induction of potentiation for this enhancement to occur. An enhancement of LTP was not observed if a non-metabolizable inositol 1,4,5-trisphosphate (InsP3) analogue (2,3-dideoxy-1,4,5-trisphosphate, 100 microM) was applied intracellularly. 3. Current-voltage relations of NMDA receptor-mediated EPSCs were not altered by InsP4 application. The presence of InsP4 was slightly effective in relieving a D-(-)-2-amino-5-phosphonopentanoic acid (D-APV)-induced block of LTP. 4. The peak current amplitude of voltage-gated calcium channels (VGCCs) was increased by InsP4. omega-Conotoxin GVIA inhibited the InsP4-induced LTP facilitation. 5. These data indicate that InsP4 can modify the extracellular Ca2+ entry through upregulation of VGCCs, which may in turn contribute to the observed enhancement of LTP induced by InsP4. 6. To investigate the possible involvement of intracellular Ca2+ release in the facilitatory effect of InsP4 on LTP, different inhibitors of the endoplasmic reticulum-dependent Ca2+ release were applied (heparin, ryanodine, cyclopiazonic acid). The results suggest that InsP4 activates postsynaptic InsP3-dependent Ca2+ release which normally does not contribute to the calcium-induced calcium release-dependent LTP.  (+info)

The regulation of transmitter release at the neuromuscular junction is tightly regulated by the influx of calcium in the presynaptic nerve terminal. Interestingly, the probability that release sites at the neuromuscular junction will liberate transmitter during each action potential is very low. The reasons for this low probability of release are not well understood. To test the hypothesis that individual N-type calcium channels open with a low probability, single channel recordings of N-type voltage-gated calcium channels were performed. Using this approach I determined the conductance of these channels, their probability of gating during an action potential waveform, and the magnitude of calcium flux during a single channel opening. I conclude from these studies that N-type voltage-gated calcium channels have a very low probability of opening (< 5%) during an action potential and the characteristics of calcium entry during single channel openings can help to explain the low probability of ...
Define N-Channel. N-Channel synonyms, N-Channel pronunciation, N-Channel translation, English dictionary definition of N-Channel. n. A type of semiconductor field effect transistor used in integrated circuit technology that consumes very little power and can be highly miniaturized....
N-type calcium channels are voltage gated calcium channels that are distributed throughout the entire body. These channels are high voltage activated channels composed of alpha-1B subunits. The alpha subunit forms the pore through which the calcium enters and helps to determine most of the channels properties. The alpha subunit is also known as the calcium channel/voltage dependent/N type, alpha 1 subunit (CACNA1B), or Cav2.2 which is used in therapeutic processes), which in humans is encoded by the CACNA1B gene. They also contain associated subunits such as β1, β3, β4, α2δ, and possibly γ. These channels are known for their importance in the nervous system. They play a small role in the migration of immature neurons before the establishment of their mature synapses, and they are critically involved in the release of neurotransmitters, which is also similar to another type of calcium channels, known as P-type calcium channels. N-type calcium channels are targets for the development of ...
N-Type Calcium Channels: CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.
We identified four properties that reduced N-channel Po at depolarized voltages. These properties were null sweeps, low Po gating, inactivation, and slow activation. Several of these gating processes behaved in a manner consistent with the modal hypothesis. In particular, null sweeps were significantly clustered in the majority of our single N-channel patches. Clustering of null records has been reported for L-type calcium channels (Hess et al., 1984), skeletal muscle sodium channels (Horn et al., 1994), and N-type calcium channels (Rittenhouse and Hess, 1994). These clustered null sweeps were interpreted to result from a gating mode from which the channel will not open. Such a mode could be represented by a long-lived inactivated state that had a mean dwell time lasting several sweep intervals (4-6 s in our recordings). Whole-cell recordings have demonstrated an inactivation process from which N-current is slow to recover (Jones and Marks, 1989b).. In three single N-channel patches, we observed ...
The control of neurotransmitter release at nerve terminals is of profound importance for neurological function and provides a powerful control system in neural networks. We show that the balance of enzymatic activities of the α isoform of the phosphatase calcineurin (CNAα) and the kinase cyclin-dependent kinase 5 (CDK5) has a dramatic influence over single action potential (AP)-driven exocytosis at nerve terminals. Acute or chronic loss of these enzymatic activities results in a sevenfold impact on single AP-driven exocytosis. We demonstrate that this control is mediated almost entirely through Cav2.2 (N-type) voltage-gated calcium channels as blocking these channels with a peptide toxin eliminates modulation by these enzymes. We found that a fraction of nerve terminals are kept in a presynaptically silent state with no measurable Ca2+ influx driven by single AP stimuli attributable to the balance of CNAα and CDK5 activities because blockade of either CNAα or CDK5 activity changes the ...
A set of fluorophenoxyanilides, designed to be simplified analogues of previously reported ω-conotoxin GVIA mimetics, were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or Cav2.2 channel is a validated target for the treatment of refractory chronic pain. Despite being significantly less complex than the originally designed mimetics, up to a seven-fold improvement in activity was observed.
Pain signaling involves transmission of nociceptive stimuli in the spinal cord where a critical balance between excitatory and inhibitory inputs determines the response to noxious stimuli. The neuropeptide, substance P (SP), mediates transmission of pain in part by binding to the tachykinin receptor (NK-1R) in the dorsal horn (DH) of the spinal cord. One of SPs downstream effects is to modulate N-type Ca2+ (N-) channels. While phospholipid breakdown is a part of the inflammatory process that accompanies tissue damage, the role of this metabolic pathway has not been completely described with respect to N-channel modulation during pain signaling. Despite the incomplete understanding of this modulation, pharmacological antagonists of both NK-1R and N-channels have been used to treat pain. In Chapter II, using whole-cell patch clamp recording techniques, the SP signaling cascade that mediates inhibition of recombinant N-channel activity was characterized. By adopting a pharmacological approach, I show that
TY - JOUR. T1 - Domain III regulates N-type (Ca V2.2) calcium channel closing kinetics. AU - Yarotskyy, Viktor. AU - Gao, Guofeng. AU - Peterson, Blaise Z.. AU - Elmslie, Keith S.. PY - 2012/4/1. Y1 - 2012/4/1. N2 - Ca V2.2 (N-type) and Ca V1.2 (L-type) calcium channels gate differently in response to membrane depolarization, which is critical to the unique physiological functions mediated by these channels. We wondered if the source for these differences could be identified. As a first step, we examined the effect of domain exchange between N-type and L-type channels on activationdeactivation kinetics, which were significantly different between these channels. Kinetic analysis of chimeric channels revealed N-channellike deactivation for all chimeric channels containing N-channel domain III, while activation appeared to be a more distributed function across domains. This led us to hypothesize that domain III was an important regulator of N-channel closing. This idea was further examined with ...
SiZ254DT Dual N-Channel 70 V (D-S) MOSFETs, available from Vishay Intertechnology, a global manufacturer of electronic components.
SQS966ENW Automotive Dual N-Channel 60 V (D-S) 175 C MOSFET, available from Vishay Intertechnology, a global manufacturer of electronic components.
STL220N6F7 - N-channel 60 V, 0.0012 Ohm typ., 120 A STripFET F7 Power MOSFET in a PowerFLAT 5x6 package, STL220N6F7, STMicroelectronics
Silicon Standard SSM95T06GS | MOSFET. SSM95T06GP,S N-CHANNEL ENHANCEMENT-MODE POWER MOSFET Low gate-charge Simple drive requirement Fast .
Neuromed Pharmaceuticals Ltd. and Merck & Co., Inc. announced that they have signed a research collaboration and license agreement to research, develop and commercialize novel compounds for the tr ...
TY - JOUR. T1 - Protein inhibition by microinjection and RNA-mediated interference in tissue culture cells. T2 - complementary approaches to study protein function.. AU - Stout, Jane R.. AU - Rizk, Rania S.. AU - Walczak, Claire. PY - 2009. Y1 - 2009. N2 - A major goal in cell biology is to understand the molecular mechanisms of the biological process under study, which requires functional information about the roles of individual proteins in the cell. For many non-genetic model organisms researchers have relied on the use of inhibitory reagents, such as antibodies that can be microinjected into cells. More recently, the advent of RNA-mediated interference (RNAi) has allowed scientists to knockdown individual proteins and to examine the consequences of the knockdown. In this chapter we present a comparison between microinjection of inhibitory reagents and RNAi for the analysis of protein function in mammalian tissue culture cells, providing both a description of the techniques as well as a ...
DMN2023UCB4 N-CHANNEL ENHANCEMENT MODE FIELD MOSFET Product Summary Features V(BR)DSS RSS(ON) Package 24V 26mΩ @ VGS = 4.5V X1-WLB1818-4     IS TA = +25°C 6.0A Built-in G-S Protection Diode Against ESD 2kV HBM Totally Lead-Free & Fully RoHS Compliant (Notes 1 & 2) Halogen and Antimony Free. Green Device (Note 3) Qualified to AEC-Q101 Standards for High Reliability Description This new generation MOSFET is designed to minimize the on-state resistance (RDS(ON)) with thin WLCSP packaging process and yet maintain superior switching performance, making it ideal for high efficiency power management applications. Mechanical Data    Case: X1-WLB1818-4 Moisture Sensitivity: Level 1 per J-STD-020 Terminal Connections: See Diagram Applications    Battery Management Load Switch Battery Protection X1-WLB1818-4 G1 G2 ESD PROTECTED TO 2kV N-Channel S1 Top View N-Channel S2 Equivalent Circuit Ordering Information (Note 4) Part Number DMN2023UCB4-7 Notes: Case X1-WLB1818-4 ...
N-type calcium channel calcium channel, voltage-dependent, N type, alpha 1B subunit Identifiers Symbol CACNA1B Alt. Symbols CACNL1A5 Entrez 774 HUGO 1389 OMIM
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Hello Hardware freaks, as an output driver I want to use a (dual) N-channel MOSFETs, a IRF7530, see http://www.irf.com/product-info/datasheets/data/irf7530.pdf.
Alternative splicing is known to generate multiple functionally distinct calcium channel variants that exhibit unique spatial and temporal expression patterns. In humans, naturally occurring mutations in genes encoding calcium channel pore forming alpha(1)-subunits are associated with several severe …
TY - JOUR. T1 - Further insights into the antinociceptive potential of a peptide disrupting the N-type calcium channel-CRMP-2 signaling complex. AU - Wilson, Sarah M.. AU - Brittain, Joel M.. AU - Piekarz, Andrew D.. AU - Ballard, Carrie J.. AU - Ripsch, Matthew S.. AU - Cummins, Theodore R.. AU - Hurley, Joyce H.. AU - Khanna, May. AU - Hammes, Nathan M.. AU - Samuels, Brian C.. AU - White, Fletcher A.. AU - Khanna, Rajesh. PY - 2011/1/1. Y1 - 2011/1/1. N2 - The N-type voltage-gated calcium channel (Ca v2.2) has gained immense prominence in the treatment of chronic pain. While decreased channel function is ultimately anti-nociceptive, directly targeting the channel can lead to multiple adverse side effects. Targeting modulators of channel activity may facilitate improved analgesic properties associated with channel block and a broader therapeutic window. A novel interaction between Ca v2.2 and collapsin response mediator protein 2 (CRMP-2) positively regulates channel function by increasing ...
Cilnidipine (INN) is a calcium channel blocker. It is a calcium antagonist accompanied with L-type and N-type calcium channel blocking functions. It was jointly developed by Fuji Viscera Pharmaceutical Company and Ajinomoto, and was approved to enter the market and be used as an anti-hypertensive in 1995.[citation needed] Unlike other calcium antagonists, cilnidipine can act on the N-type calcium channel in addition to acting on the L-type calcium channel. Cilnidipine is approved for use in Japan, China, India, Korea, and some European countries to treat hypertension. Cilnidipine decreases blood pressure and is used to treat hypertension and its comorbidities. Due to its blocking action at the N-type and L-type calcium channel, cilnidipine dilates both arterioles and venules, reducing the pressure in the capillary bed. Cilnidipine is vasoselective and has a weak direct dromotropic effect, a strong vasodepressor effect, and an arrhythmia-inhibiting effect. Blood pressure control with cilnidipine ...
L-type (CaV1.2) voltage-gated calcium channels play critical roles in membrane excitability, gene expression, cardiac and smooth muscle contraction. Alternative splicing enriches the functional diversity of the pore-forming CaV1.2 alpha-1 subunit. Systematic screening of the human CaV1.2 alpha-1 gene by the transcript-scanning method revealed 19 of the 55 exons were subjected to alternative splicing, and two of these were novel exons. A large IVS3-S4 variability resulting from combinatorial utilization of exons 31-33 demonstrated a correlation between increased IVS3-S4 linker length and more depolarized activation potentials.Sixty-four splicing profiles of CaV1.2 alpha-1 subunit were identified from 6 full-length cDNA libraries generated from heart and aortic tissues of the Spontaneously Hypertensive Rats and Wistar Kyoto Rats. The tissue-selective and pathologically induced splicing profiles of 10 alternatively spliced exons assessed indicated a striking alteration in exon utilization and ...
Among G-protein-coupled receptors, CB1Rs are unusual in that they are expressed nearly exclusively in presynaptic terminals and are excluded from the soma of adult neurons. This unique distribution pattern makes it difficult to directly examine the coupling of native CB1Rs to Ca2+ channels. Therefore heterologous expression of CB1Rs by intranuclear injection of CB1 cDNA in an isolated adult mammalian neuron that has well-studied G-protein pathways facilitates in situ investigation of CB1 receptors. In this neuronal expression system, we demonstrated that three putative endocannabinoids, AEA, 2-AG, and 2-AGE, like the cannabimimetic aminoalkylindole WIN, initiate PTX-sensitive, voltage-dependent N-type Ca2+ channel inhibition via CB1Rs.. WIN is a synthetic CB1R agonist widely used in the studies of CB1Rs, including DSI and DSE. Modulation of N-type Ca2+ channel by WIN via CB1Rs was first observed in differentiated NG108-15 neuroblastoma cells and N18 cells (Caulfield and Brown,1992; Mackie and ...
N-type calcium channels belong to the family of voltage gated calcium channels , which open in response to membrane depolarisation. These channels are responsible for the calcium influx that triggers neurotransmitter release at presynaptic terminals. N - type channels are particularly important in mediating neurotransmitter release at the presynaptic terminals of peripheral sensory neurons and have been implicated i n neuropathic pain. Understanding the regulation of N - type channels is critical to the development of treatments that target these channels. Until now it has been difficult to directly investigate the regulation of their expression at the cell surface due to the inability to selectively visualise channels at the surface. Although N - type channels are thought to consist of a Ca v 2.2, α 2 δ and β subunits, there is uncertainty over whether the pore forming Ca v 2.2 subunit does indeed interact with α 2 δ at the cell surface. The work in this thesis has yielded two tagged ...
A method of manufacturing a flash memory semiconductor device that eliminates the step of forming sidewall spacers on n-channel and p-channel transistor gate structures. Resist spacers having a dimension of Gn+2Sn are formed on n-channel transistor gate structures and an N+ implant is performed to form N+ implant is performed to form N+ regions in the n-channel substrate region. Resist spacers having a dimension of Gs +2Sp are formed on p-channel transistor gate structures and a P+ implant is performed to form P+ regions in the p-channel substrate region.
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Burke, Julian F and Thomas, Sandy (1999) Eli Lilly: DNA patenting through the ages. Expert Opinion on Therapeutic Patents, 9. pp. 119-127. ISSN 1354-3776 Cox, Brian and Denyer, Jane C (1998) N-type calcium channel blockers in pain and stroke. Expert Opinion on Therapeutic Patents, 8 (10). pp. 1237-1250. ISSN 1354-3776 ...
WORKLIST ENTRIES (1): LVDCCALPHA1D View alignment Voltage-dependent L-type calcium channel alpha-1D subunit signature Type of fingerprint: COMPOUND with 5 elements Links: PRINTS; PR00167 CACHANNEL; PR01629 TVDCCALPHA1; PR01630 LVDCCALPHA1 PRINTS; PR01631 NVDCCALPHA1; PR01632 PQVDCCALPHA1; PR01633 RVDCCALPHA1 PRINTS; PR01634 LVDCCALPHA1S; PR01635 LVDCCALPHA1C Creation date 20-DEC-2001 1. WILLIAMS, M.E., BRUST, P.F., FELDMAN, D.H., PATTHI, S., SIMERSON, S., MAROUFI, A., MCCUE, A.F., VELICELBI, G., ELLIS, S.B. AND HARPOLD, M.M. Structure and functional expression of an omega-conotoxin sensitive human N-type calcium channel. SCIENCE 257 389-395 (1992). 2. MORI, Y., FRIEDRICH, T., KIM, MS., MIKAMI, A., NAKAI, J., RUTH, P., BOSSE, E., HOFMANN, F., FLOCKERZI, V., FURUICHI, T., MIKOSHIBA, K., IMOTO, K., TANABE, T. AND NUMA, S. Primary structure and functional expression from complementary DNA of a brain calcium channel. NATURE 350 398-402 (1991). 3. ASHCROFT, F.M. Voltage-gated Ca2+ channels. IN ION ...
WORKLIST ENTRIES (1): LVDCCALPHA1C View alignment Voltage-dependent L-type calcium channel alpha-1C subunit signature Type of fingerprint: COMPOUND with 13 elements Links: PRINTS; PR00167 CACHANNEL; PR01629 TVDCCALPHA1; PR01630 LVDCCALPHA1 PRINTS; PR01631 NVDCCALPHA1; PR01632 PQVDCCALPHA1; PR01633 RVDCCALPHA1 PRINTS; PR01634 LVDCCALPHA1S; PR01636 LVDCCALPHA1D Creation date 20-DEC-2001 1. WILLIAMS, M.E., BRUST, P.F., FELDMAN, D.H., PATTHI, S., SIMERSON, S., MAROUFI, A., MCCUE, A.F., VELICELBI, G., ELLIS, S.B. AND HARPOLD, M.M. Structure and functional expression of an omega-conotoxin sensitive human N-type calcium channel. SCIENCE 257 389-395 (1992). 2. MORI, Y., FRIEDRICH, T., KIM, MS., MIKAMI, A., NAKAI, J., RUTH, P., BOSSE, E., HOFMANN, F., FLOCKERZI, V., FURUICHI, T., MIKOSHIBA, K., IMOTO, K., TANABE, T. AND NUMA, S. Primary structure and functional expression from complementary DNA of a brain calcium channel. NATURE 350 398-402 (1991). 3. ASHCROFT, F.M. Voltage-gated Ca2+ channels. IN ION ...
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
SuperFET® III MOSFET is ON Semiconductors brand-new high voltage super-junction (SJ) MOSFET family that is utilizing charge balance technology for
APM3007NU N-Channel Enhancement Mode MOSFET Features • Pin Description 30V/50A, RDS(ON)=5.5mΩ (typ.) @ VGS=10V RDS(ON)=8.5mΩ (typ.) @ VGS=4.5V • • • G Super High Dense Cell Design D S Reliable and Rugged Top View of TO-252 Lead Free Available (RoHS Compliant) D Applications • Power Management in Desktop Computer or G DC/DC Converters S N-Channel MOSFET Ordering and Marking Information Package Code U : TO-252 Operating Junction Temp. Range C : -55 to 150 ° C Handling Code TU : Tube TR : Tape & Reel Lead Free Code L : Lead Free Device Blank : Original Device APM3007N Lead Free Code Handling Code Temp. Range Package Code APM3007N U : APM3007N XXXXX XXXXX - Date Code Note: ANPEC lead-free products contain molding compounds and 100% matte tin plate termination finish; which are fully compliant with RoHS and compatible with both SnPb and lead-free soldiering operations. ANPEC lead-free products meet or exceed the lead-free requirements of IPC/JEDEC J STD-020C for MSL classification at ...
The FDMS7658AS has been designed to minimize losses in power conversion application. Advancements in both silicon and package technologies have been combined
Fuji Electric KMR datasheet, 2SKMR (1-page), KMR datasheet, KMR pdf, KMR datasheet pdf, KMR pinouts. 2SKMR Datasheet (PDF). SizeK _fuji. 2SKMR. N-channel MOS-FET 2SKMR FAP-IIS Series V 2, 5Ω 6A. K DATASHEET DOWNLOAD - K Datasheet: N-channel MOS-FET / V / 6A / 50W, K PDF VIEW Download Fuji Electric, K 1 page Datasheet. Author: […]. Read More ...
New genetic data have allowed a more precise definition of Familial hemiplegic migraine (FHM) than was possible previously. Specific genetic subtypes have been identified: in FHM1 there are mutations in the CACNA1A gene (coding for a calcium channel) on chromosome 19; in FHM2 there are mutations in the ATP1A2 gene (coding for a K/Na-ATPase) on chromosome 1; and in FHM3 there are mutations in the SCN1A gene (coding for a sodium channel) on chromosome 2. There may be other loci not yet identified. If genetic testing is done, the genetic subtype (if discovered) should be specified at the fifth digit.. It has been shown that Familial hemiplegic migraine (FHM) very often presents with brainstem symptoms in addition to the typical aura symptoms, and that headache almost always occurs. Rarely, during FHM attacks, disturbances of consciousness (sometimes including coma), confusion, fever and CSF pleocytosis can occur.. Familial hemiplegic migraine (FHM) may be mistaken for ...
Among various types of low- and high-threshold calcium channels, the high voltage-activated P/Q-type channel is the most abundant in the cerebellum. These P/Q-type channels are involved in the regulation of neurotransmitter release and in the integration of dendritic inputs. We used an antibody specific for the α1A subunit of the P/Q-type channel in quantitative pre-embedding immunogold labelling combined with three-dimensional reconstruction to reveal the subcellular distribution of pre- and postsynaptic P/Q-type channels in the rat cerebellum. At the light microscopic level, immunoreactivity for the α1A protein was prevalent in the molecular layer, whereas immunostaining was moderate in the somata of Purkinje cells and weak in the granule cell layer. At the electron microscopic level, the most intense Immunoreactivity for the α1A subunit was found in the presynaptic active zone of parallel fibre varicosities. The dendritic spines of Purkinje cells were also strongly labelled with the ...
Objectives Clinical studies have indicated the beneficial effect of an L/N-type calcium channel blocker (CCB) cilnidipine around the progression of proteinuria in hypertensive patients compared with an L-type CCB amlodipine. in an age-dependent manner. Cilnidipine suppressed the proteinuria greater than amlodipine did. The immunohistochemical analysis showed that N-type calcium channel and Wilms tumor factor a marker of podocyte were co-expressed. SHR/ND had significantly greater desmin staining an indication of podocyte injury with lower podocin and nephrin expression in the glomeruli than Wistar-Kyoto rat or SHR. Cilnidipine significantly prevented the increase in desmin staining and restored the glomerular podocin and nephrin expression compared with amlodipine. Cilnidipine also prevented the increase in renal angiotensin II content the expression and membrane translocation of NADPH oxidase subunits and dihydroethidium staining in SHR/ND. In contrast amlodipine failed MUC12 to switch these ...
Highly selective N-type voltage-gated calcium (CaV) channel inhibitors from cone snail venom (the ω-conotoxins) have emerged as a new class of therapeutics for the treatment of chronic and neuropathic pain. Earlier in 2005, Prialt (Elan) or synthetic ω-conotoxin MVIIA, was the first ω-conotoxin to be approved by Food and Drug Administration for human use. This review compares the action of three ω-conotoxins, GVIA, MVIIA and CVID, describing their structure-activity relationships and potential as leads for the design of improved N-type therapeutics that are more useful in the treatment of chronic pain.
The use of organotypic hippocampal-slice cultures to investigate neuronal damage after ischemia or hypoxia presents an ideal model for the study of direct neuronal protective effects of calcium channel antagonists. The cultures retain many of the organizational features of the in vivo hippocampus without a functional vascular component, and thus only neuronal effects of the drugs are observed. Using this model, we have demonstrated a clear concentration-dependent reduction in hypoxia-induced neuronal death by CTX MVIIA. At a concentration of 300 nmol/L, CTX MVIIC was equipotent compared with CTX MVIIA. Neither nifedipine nor SB201823-A was neuroprotective. Neuronal damage induced by ischemia was not prevented by any of the compounds.. It has previously been demonstrated in vivo that CTX MVIIA, but not CTX MVIIC, has potent neuroprotective actions, even when administered many hours after an ischemic episode.11 23 In vitro, delaying the addition of CTX MVIIA until immediately after the hypoxic ...
Voltage-dependent N-type calcium channel subunit alpha-1B (Brain calcium channel III) (BIII) (Calcium channel; L type; alpha-1 polypeptide isoform 5) (Voltage-gated calcium channel subunit alpha Cav2.2 ...
Fig. 9 - Maximum Drain Current vs. Case TemperatureFig. 10a - Switching Time Test CircuitFig. 10b - Switching Time WaveformsFig. 11 - Maximum Effective Transient Thermal Impedance, Junction-to-CaseFig. 12a - Unclamped Inductive Test CircuitFig. 12b - Unclamped Inductive Waveforms255075100 datasheet search, datasheets, Datasheet search site for Electronic Components and Semiconductors, integrated circuits, diodes and other semiconductors.
RGK regulation of voltage-gated calcium channels. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
ID A0A151MF56_ALLMI Unreviewed; 2363 AA. AC A0A151MF56; DT 08-JUN-2016, integrated into UniProtKB/TrEMBL. DT 08-JUN-2016, sequence version 1. DT 25-OCT-2017, entry version 11. DE RecName: Full=Voltage-dependent N-type calcium channel subunit alpha {ECO:0000256,RuleBase:RU003808}; GN ORFNames=Y1Q_0005596 {ECO:0000313,EMBL:KYO23157.1}; OS Alligator mississippiensis (American alligator). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Archelosauria; Archosauria; Crocodylia; Alligatoridae; Alligatorinae; OC Alligator. OX NCBI_TaxID=8496 {ECO:0000313,EMBL:KYO23157.1}; RN [1] {ECO:0000313,EMBL:KYO23157.1, ECO:0000313,Proteomes:UP000050525} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=KSC_2009_1 {ECO:0000313,EMBL:KYO23157.1}; RX PubMed=22293439; DOI=10.1186/gb-2012-13-1-415; RA St John J.A., Braun E.L., Isberg S.R., Miles L.G., Chong A.Y., RA Gongora J., Dalzell P., Moran C., Bedhom B., Abzhanov A., RA Burgess S.C., Cooksey A.M., Castoe T.A., Crawford N.G., ...
Animals. The generation and detailed characterization of Cav1.2DHP(-/-) and Cav1.3(-/-) mice has been reported previously (Platzer et al., 2000; Sinnegger-Brauns et al., 2004). Double mutant Cav1.2DHP(-/-) × Cav1.3(-/-) mice were generated by crossing Cav1.3(-/-) male mice with Cav1.2DHP(-/-) female mice previously backcrossed into C57BL/6N background in five generations. Animals heterozygous for both mutant alleles were then crossed to obtain homozygous double mutants (referred to as Cav-DM). Tissues and RNA from 3- to 16-month old male mice or 3- to 12-month old male Sprague-Dawley rats were used for experiments. Animal handling was approved by the Bundesministerium für Bildung, Wissenschaft und Kultur (Vienna, Austria) in accordance with international laws and policies of animal welfare.. Recombinant α1 cDNAs. The following α1 subunit cDNAs were used (GenBank accession numbers given in parentheses): rabbit Cav1.2 (X15539), human Cav1.3 (EU63339; Koschak et al., 2001), and human Cav1.4 ...
We have used all reasonable efforts to ensure that the information displayed on these pages and contained in the databases is of high quality. We make no warranty, express or implied, as to its accuracy or that the information is fit for a particular purpose, and will not be held responsible for any consequences arising out of any inaccuracies or omissions. Individuals, organisations and companies which use this database do so on the understanding that no liability whatsoever either direct or indirect shall rest upon the curator(s) or any of their employees or agents for the effects of any product, process or method that may be produced or adopted by any part, notwithstanding that the formulation of such product, process or method may be based upon information here provided ...
Ulises Meza, Ashish Thapliyal, Roger A Bannister, Brett A Adams. Mol. Pharmacol., 2007 Jan , 71, 284-93. Neurokinin (NK) 1 receptors and CaV2.3 calcium channels are both expressed in nociceptive neurons, and mice lacking either protein display altered responses to noxious stimuli. Here, we examined modulation of CaV2.3 through NK1 receptors expressed in human embryonic kidney 293 cells. We find that NK1 receptors generate complex modulation of CaV2.3. In particular, weak activation of these receptors evokes mainly stimulation of CaV2.3, whereas strong receptor activation elicits profound inhibition that overlaps with channel stimulation. Unlike R-type channels encoded by CaV2.3, L-type (CaV1.3), N-type (CaV2.2), and P/Q-type (CaV2.1) channels are inhibited, but not stimulated, through NK1 receptors. Pharmacological experiments show that protein kinase C (PKC) mediates stimulation of CaV2.3 through NK1 receptors. The signaling mechanisms underlying inhibition were explored by expressing proteins ...
There are two interrelated factors that control the performance of a FET (i.e., current flow through the embedded channel): the voltage between the gate and source (Vgs); and the voltage from drain-to-source (Vds). If the gate-to-source voltage is at ground (zero volts) with he drain connected to a positive voltage and the source tied to ground, the electron shortage in the channel restricts the amount of current that can flow through the channel. The only way to increase current flow is to increase the drain-to-source voltage.. Lets take a look at what happens when a signal source is connected to the gate of a FET and a positive voltage is applied to the drain (refer to Fig. 2A). If a positive voltage is applied to the drain and a negative voltage is applied to the source with the gate terminal open, a drain current flows.. When the gate is biased negative with respect to the source, the PN junction is reverse biased, which causes a depletion region to form. Because the N-channel is more ...
After contact holes for the P- and N-type source or drain regions of P- and N-channel MOSFETs have been made at a common step, an N-type impurity is ion-implanted into at least the N-type source or drain regions through the contact holes. The N-type impurity is annealed to fornm an N-type region which is deeper than the N-type source or drain regions. During the annealing treatment, the N-type source or drain regions are covered with an insulating film.
A CMOS device wherein the N-channel devices have n+ gates, and the P-channel devices have p+ gates. A TiN local interconnect system is used to connect the two types of gates, as well as providing connections to moat.
ST Microelectronics STW55NE10 datasheet, N-CHANNEL MOSFET (1-page), STW55NE10 datasheet, STW55NE10 pdf, STW55NE10 datasheet pdf, STW55NE10 pinouts
Raffaella G., Sole,C., Llecha,N, Segura, M.F., Moubarak,R., Iglesias-Guimarais,V., Perez-Garcia,M.J., Reix,S., Zhang,J., Badiola,N., Sanchis,D., Rodriguez-Alvarez,J.,Trullas,R., Yuste,V.J., and J.X. Comella ...
... inhibits N-type calcium channels. The concentration of piracetam achieved in central nervous system after a typical ... is much higher than the concentration necessary to inhibit N-type calcium channels (IC50 of piracetam in rat neurons was 3 μM ... Piracetam may exert its global effect on brain neurotransmission via modulation of ion channels (i.e., Na+, K+). It has been ... It is hypothesized to act on ion channels or ion carriers, thus leading to increased neuron excitability. GABA brain metabolism ...
Unlike other calcium antagonists, cilnidipine can act on the N-type calcium channel in addition to acting on the L-type calcium ... It is a calcium antagonist accompanied with L-type and N-type calcium channel blocking functions. ... Due to its blocking action at the N-type and L-type calcium channel, cilnidipine dilates both arterioles and venules, reducing ... May 2002). "Cilnidipine is a novel slow-acting blocker of vascular L-type calcium channels that does not target protein kinase ...
"Osteoprotegerin expression and secretion are regulated by calcium influx through the L-type voltage-sensitive calcium channel ... This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ... Calcium channel, voltage-dependent, L type, alpha 1C subunit (also known as Cav1.2) is a protein that in humans is encoded by ... Calcium channel Calcium channel associated transcriptional regulator ENSG00000285479 GRCh38: Ensembl release 89: ...
"Molecular characterization of T-type calcium channels". Cell Calcium. 40 (2): 89-96. doi:10.1016/j.ceca.2006.04.012. PMID ... Seizures are believed to originate in the thalamus, where there is an abundance of T-type calcium channels such as those ... a T-type calcium channel". J Neurosci. 25 (19): 4844-55. doi:10.1523/JNEUROSCI.0847-05.2005. PMC 6724770. PMID 15888660. Liang ... "Gating effects of mutations in the Cav3.2 T-type calcium channel associated with childhood absence epilepsy". J Biol Chem. 279 ...
... inhibits P-type calcium channels Botulinum toxin: inhibits SNARE proteins Calcium channel blockers (nifedipine, diltiazem) do ... and thereby affecting P-type calcium channels): Antibiotics (clindamycin, polymyxin) Magnesium: antagonizes P-type calcium ... Nicotinic receptors come in two main types, known as muscle-type and neuronal-type. The muscle-type can be selectively blocked ... These drugs affect L-type calcium channels. The autonomic nervous system controls a wide range of involuntary and unconscious ...
... reversibly blocks N-type calcium channels. In addition, it has a low affinity for L or P/Q-type channels. The mechanism by ... Ptu1 is a toxin that can reversibly bind N-type calcium channels. Its isolated from the assassin bug Peirates turpis. The toxin ... Second, Ptu1 has a relatively low binding affinity for N-type calcium channels compared to MVIIA. A possible explanation for ... a toxin from the assassin bug Peirates turpis that blocks the voltage-sensitive calcium channel N-type". Biochemistry. 40 (43 ...
The α1B protein, together with β and α2δ subunits forms N-type calcium channel (Cav2.2 channel) PMID 26386135 GRCh38: Ensembl ... subunits for the calcium channel I-II linker in relation to calcium channel function". The Journal of Physiology. 574 (Pt 2): ... "Entrez Gene: CACNA1B calcium channel, voltage-dependent, N type, alpha 1B subunit". Diriong S, Lory P, Williams ME, Ellis SB, ... The voltage-dependent N-type calcium channel subunit alpha-1B is a protein that in humans is encoded by the CACNA1B gene. ...
Cav3.1 is a type of low-voltage-activated calcium channel, also known as "T-type" for its transient on and off. It is expressed ... Calcium channel, voltage-dependent, T type, alpha 1G subunit, also known as CACNA1G or Cav3.1 is a protein which in humans is ... "Entrez Gene: CACNA1H calcium channel, voltage-dependent, T type, alpha 1H subunit". Perez-Reyes E, Cribbs LL, Daud A, Lacerda ... Kopecky, Benjamin J.; Liang, Ruqiang; Bao, Jianxin (2014). "T-type Calcium Channel Blockers as Neuroprotective Agents". ...
... is classified as a selective antagonist of T-type voltage-operated calcium ion channels, because its binding blocks ... Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group.[1] It is prescribed for ... Arab SF, Düwel P, Jüngling E, Westhofen M, Lückhoff A (June 2004). "Inhibition of voltage-gated calcium currents in type II ... hypothesized that cinnarizine exerts its effects by inhibiting the calcium currents in voltage gated channels in type II ...
Voltage-dependent calcium channel gamma-3 subunit is a protein that in humans is encoded by the CACNG3 gene. L-type calcium ... This gene is a member of the neuronal calcium channel gamma subunit gene subfamily of the PMP-22/EMP/MP20 family. This gene is ... "Entrez Gene: CACNG3 calcium channel, voltage-dependent, gamma subunit 3". Powers PA, Liu S, Hogan K, Gregg RG (1993). " ... It is an integral membrane protein that is thought to stabilize the calcium channel in an inactive (closed) state. This protein ...
"Entrez Gene: CACNA1F calcium channel, voltage-dependent, L type, alpha 1F subunit". Catterall WA, Perez-Reyes E, Snutch TP, ... a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell ... 1998). "An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness". Nat. Genet. 19 (3 ... Cav1.4 also known as the calcium channel, voltage-dependent, L type, alpha 1F subunit (CACNA1F), is a human gene. This gene ...
Voltage-dependent calcium channel gamma-1 subunit is a protein that in humans is encoded by the CACNG1 gene. L-type calcium ... 1993). "Localization of the gamma-subunit of the skeletal muscle L-type voltage-dependent calcium channel gene (CACNLG) to ... and gamma-subunits of the human skeletal muscle L-type voltage-dependent calcium channel on chromosome 17q and exclusion as ... This gene is a member of the neuronal calcium channel gamma subunit gene subfamily of the PMP-22/EMP/MP20 family and is located ...
Voltage-dependent calcium channel gamma-4 subunit is a protein that in humans is encoded by the CACNG4 gene. L-type calcium ... This gene is a member of the neuronal calcium channel gamma subunit gene subfamily of the PMP-22/EMP/MP20 family and is located ... "Entrez Gene: CACNG4 calcium channel, voltage-dependent, gamma subunit 4". Gerhard DS, Wagner L, Feingold EA, et al. (2004). " ... Voltage-dependent calcium channel GRCh38: Ensembl release 89: ENSG00000075461 - Ensembl, May 2017 GRCm38: Ensembl release 89: ...
L-type calcium channels are composed of five subunits. The protein encoded by this gene represents one of these subunits, gamma ... Calcium channel, voltage-dependent, gamma subunit 2, also known as CACNG2 or stargazin is a protein that in humans is encoded ... "Entrez Gene: CACNG2 calcium channel, voltage-dependent, gamma subunit 2". Brandler WM, Antaki D, Gujral M, Noor A, Rosanio G, ... This gene is a member of the neuronal calcium channel gamma subunit gene subfamily of the PMP-22/EMP/MP20 family. Stargazin is ...
... is a cardioselective L-type calcium channel blocker. AH-1058 binds to the same sites on the alpha-1 subunit of L-type ... These sites on the alpha-1 subunit differ from the active site of the calcium channel, meaning AH-1058 binds L-type calcium ... L-type calcium channel blockers). Class I antiarrhythmic (sodium channel blocker) characteristics have also been seen, but the ... In addition AH-1058 appears to interact with multiple states of L-type calcium channels (i.e. resting and inactive) to suppress ...
... is a calcium channel blocker. Lacroix P, Linee P, Forest MC (January 1991). "Diproteverine (BRL 40015): a new type of calcium ...
... calcium channel blocker, inhibits both L-type and T-type calcium channels. Efonidipine exhibits antihypertensive effect through ... It was launched in 1995, under the brand name Landel (ランデル). The drug blocks both T-type and L-type calcium channels. Drug ... Working on sino atrial node cells by inhibiting T-type calcium channel activation, Efonidipine prolongs the late phase-4 ... Efonidipine increases coronary blood flow by blocking L & T-type calcium channels and attenuates myocardial ischaemia. By ...
SLC30A1 modulates zinc permeation through the L-type calcium channel. SLC30A1 downregulates not only Zn++ influx, but also Ca++ ...
Cheng RC, Tikhonov DB, Zhorov BS (October 2009). "Structural model for phenylalkylamine binding to L-type calcium channels". ... Cheng RC, Tikhonov DB, Zhorov BS (October 2009). "Structural model for phenylalkylamine binding to L-type calcium channels". ... "L-type Ca2+ channel antagonists block voltage-dependent Ca2+ channels in identified leech neurons". Brain Research. 1013 (2): ... Devapamil is a calcium channel blocker. It is also known as desmethoxyverapamil, which is a phenylalkylamine (PAA) derivative. ...
Proximal muscle weakness is a product of pathogenic autoantibodies directed against P/Q-type voltage-gated calcium channels, ... which activates voltage-gated calcium channels to allow calcium ions to enter the neuron. Calcium ions bind to sensor proteins ... This type of tumor also expresses voltage-gated calcium channels. Oftentimes, LEMS also occurs alongside myasthenia gravis. ... by lengthening the time that voltage-gated calcium channels remain open after blocking voltage-gated potassium channels. In the ...
It is a calcium channel blocker of the dihydropyridine type. Nifedipine is taken by mouth and comes in fast- and slow-release ... Although nifedipine and other dihydropyridines are commonly regarded as specific to the L-type calcium channel, they also ... As calcium channel blocker, nifedipine has a risk of causing gingival hyperplasia A number of persons have developed toxicity ... Nifedipine, sold under the brand name Adalat among others, is a calcium channel blocker medication used to manage angina, high ...
The T-type calcium channel is found in neurons throughout the brain. These channels produce particularly large currents in ... Recent research has also been conducted on the T-type calcium channel and how modulation of these channels may allow for the ... Antiepileptic drugs can control absence seizures by inhibiting the T-type calcium channels which prevents low-voltage calcium ... T-type calcium channels have been known to play a role in the spike-and-wave discharges of absence seizures. ...
Sodium channel, voltage-gated, type XI, alpha subunit also known as SCN11A or Nav1.9 is a voltage-gated sodium ion channel ... Nomenclature and structure-function relationships of voltage-gated calcium channels". Pharmacological Reviews. 57 (4): 411-25. ... "Entrez Gene: Sodium channel, voltage-gated, type XI, alpha subunit". Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J ( ... This property is found in similar channels, namely Nav1.8, and has been associated with slower channel kinetics than the ...
Structural model for phenylalkylamine binding to L-type calcium channels. The Journal of Biological Chemistry, 284(41), 28332- ... The drug targets L-type Ca+2 channels, and decreases conduction in cells where Ca+2 is required for action potential upstroke ( ... 1995). Electrophysiological effect of BRL-32872, a novel antiarrhythmic agent with potassium and calcium channel blocking ... BRL-32872's class III activity is directed towards the human ether-a-go-go-related gene (hERG) K+ channel. hERG channels are ...
Ritz, Beate; Rhodes, Shannon L; Qian, Lei; Schernhammer, Eva; Olsen, Jorgen; Friis, Soren (2009). "L-type calcium channel ... Lang, Yakun; Gong, Dandan; Fan, Yu (2015). "Calcium channel blocker use and risk of Parkinson's disease: A meta-analysis". ... Gudala, Kapil; Kanukula, Raju; Bansal, Dipika (2015). "Reduced Risk of Parkinson's Disease in Users of Calcium Channel Blockers ... Pasternak, Björn; Svanström, Henrik; Nielsen, Nete M; Fugger, Lars; Melbye, Mads; Hviid, Anders (2012). "Use of Calcium Channel ...
"Structure-activity relationships for P-type calcium channel-selective omega-agatoxins". Nat. Struct. Biol. 1 (12): 853-6. doi: ... The mechanism of many spider toxins is through blockage of calcium channels. A remotely related group of atracotoxins operate ... consensus molecular folding of calcium channel blockers". J. Mol. Biol. 250 (5): 659-71. doi:10.1006/jmbi.1995.0406. PMID ... "Three-dimensional solution structure of the calcium channel antagonist omega-agatoxin IVA: ...
... type-1) and atypical (type-2). They are both caused by mutations in CACNA1C, the gene encoding the calcium channel Cav1.2 α ... With the characterization of Timothy syndrome mutations indicating that they cause defects in calcium currents, calcium channel ... "Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations". Proc Natl Acad Sci USA. 102 (23): 8089-8096. ... However, it was linked with calcium channel abnormalities in 2004, and the disorder was thence named "Timothy syndrome" in ...
Treatment of the allergic event alone can abolish type I variant. Giving vasodilators such as nitroglycerin or calcium channel ... Three variants of Kounis syndrome were found and a study concluded that type 1 variant was most commonly seen followed by type ... Acute coronary event protocol is applied and type II can be treated similarly to type I for cardiac symptom control. Glucagon ... Type III is subdivided now to stent thrombosis (subtype a) and stent restenosis (subtype b). The management of these patients ...
... calcium channels (L-Type). It is the first positive inotropic agent shown to act specifically and directly on calcium channels ... Bay K8644 is a chemical compound that functions as a calcium channel agonist. Bay K8644 is used primarily as a biochemical ... that enhances calcium currents in guinea pig and calf myocardial cells. A new type of positive inotropic agent". Circ Res. 56 ( ...
Mason, R.P.; Marche, P.; Hintze, T.H. (December 2003). "Novel Vascular Biology of Third-Generation L-Type Calcium Channel ... Calcium channel blockers are medications that prevent the movement of calcium ions across calcium channels. They can be used to ... Amlodipine, hydralazine and dihydropyridine are examples of calcium channel blockers. Other medications such as angiotensin- ... Common types of aneurysm include abdominal aortic aneurysm, thoracic aortic aneurysm and intracranial aneurysm. Most types of ...
Models of this type are typically built in large simulation platforms like GENESIS or NEURON. There have been some attempts to ... With the emergence of two-photon microscopy and calcium imaging, we now have powerful experimental methods with which to test ... Voltage sensitive ion channels are glycoprotein molecules which extend through the lipid bilayer, allowing ions to traverse ... "Intracellular Calcium Dynamics Permit a Purkinje Neuron Model to Perform Toggle and Gain Computations Upon its Inputs" ...
The type of leaf is usually characteristic of a species (monomorphic), although some species produce more than one type of leaf ... Veins sunken below the surface, resulting in a rounded channel. Sometimes confused with "guttered" because the channels may ... Cote, G. G. (2009). "Diversity and distribution of idioblasts producing calcium oxalate crystals in Dieffenbachia seguine ( ... Analyses of vein patterns often fall into consideration of the vein orders, primary vein type, secondary vein type (major veins ...
Other research has also suggested that calcium flow through N-type calcium channels is essential for normal breathing, and is ... L-type calcium channels are known to increase the frequency of action potentials in some neurons, which might be the reason ... P/Q-type calcium channels are mainly responsible for the release of neurotransmitters that excite, or activate, postsynaptic ... Fictive sigh depends critically on synaptic mechanisms that involve P/Q type calcium channels, suggestive of a subset of ...
... which opens ion channels (largely sodium channels, though calcium can enter through these channels as well). The positive ... One type of photosensitive pigment Three types of photosensitive pigment in humans ... This change in the cell's membrane potential causes voltage-gated calcium channels to close. This leads to a decrease in the ... A decrease in the intracellular calcium concentration means that less glutamate is released via calcium-induced exocytosis to ...
The microscopic structure of conifer wood consists of two types of cells: parenchyma, which have an oval or polyhedral shape ... The eggs hatch in about 2 weeks, and the tiny larvae tunnel to the wood and score its surface with their feeding channels. With ... calcium, magnesium, and sulfur, all used in relatively large amounts (Buckman and Brady 1969).[31] Nutrient concentrations in ... All three types or reproductive cycles have a long gap in between pollination and fertilization. ...
Calcium Scandium Titanium Vanadium Chromium Manganese Iron Cobalt Nickel Copper Zinc Gallium Germanium Arsenic Selenium Bromine ... They form various types of oxides, such as simple oxides (containing the O2− ion), peroxides (containing the O2−. 2 ion, where ... Hellgren, Mikko; Sandberg, Lars; Edholm, Olle (2006). "A comparison between two prokaryotic potassium channels (KirBac1.1 and ... A wheel type radiotherapy device which has a long collimator to focus the radiation into a narrow beam. The caesium-137 ...
... is a hypothesized type of nuclear reaction that would occur at, or near, room temperature. This is compared with ... 265-268 "(...) the equality of the two channels is known to be preserved from high energy through 20 keV and down to about 5 ... Several medium and heavy elements like calcium, titanium, chromium, manganese, iron, cobalt, copper and zinc have been reported ... Nuclear fusion of the type postulated would be inconsistent with current understanding and, if verified, would require ...
The link was a single nucleotide polymorphism of two genes involved in calcium channel signaling with neurons. One of these ... Phenylalanine is ingested through food, so a diet should decrease types of foods that have high amounts of phenylalanine. Foods ... Both males and females with larger combs have higher bone density and strength, which allows females to deposit more calcium ... the part of the bone that transfers calcium into developing eggshells) are located at the same locus as the gene affecting comb ...
Diets of this type include NCEP Step I and II. A meta-analysis of 16 trials of 2-12 months' duration found that low-fat diets ( ... "Mitochondrial Ion Channels: Gatekeepers of Life and Death". Physiology. 20 (5): 303-315. doi:10.1152/physiol.00020.2005. ISSN ... The American Diabetes Association recommended a low carbohydrate diet to reduce weight for those with or at risk of Type 2 ... Trapp, Caroline B.; Barnard, Neal D. (2010-04-01). "Usefulness of vegetarian and vegan diets for treating type 2 diabetes". ...
calcium channel activity. • aspartic-type endopeptidase activity. • endopeptidase activity. • hydrolase activity. • aspartic ... The study showed that presenilin-1 is down regulated in cell type while it is overexpressed in the other cell type.[27] Another ... endoplasmic reticulum calcium ion homeostasis. • response to oxidative stress. • autophagosome assembly. • positive regulation ... smooth endoplasmic reticulum calcium ion homeostasis. • synaptic vesicle targeting. • Cajal-Retzius cell differentiation. • ...
They include the myoga (Zingiber mioga), the several types of galangal, the fingerroot (Boesenbergia rotunda), and the bitter ... States in which ginger is exported follow the marketing channels of vegetable marketing in India, and the steps are similar to ... Ginger has the ability to grow in a wide variety of land types and areas, however is best produced when grown in a warm, humid ... On the island of Corfu, Greece, a traditional drink called τσιτσιμπύρα (tsitsibira), a type of ginger beer, is made. The people ...
embryonic camera-type eye morphogenesis. • post-embryonic camera-type eye development. • positive regulation of T cell cytokine ... Wnt signaling pathway, calcium modulating pathway. • Wnt signaling pathway, planar cell polarity pathway. • beta-catenin ... "IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.. ... embryonic camera-type eye development. • multicellular organism development. • cell surface receptor signaling pathway. • ...
Calcium supports child growth in many varying ways. Common sources of calcium are found in dates, grapefruit,oranges, celery, ... Better Health Channel. 2015-02-09. Retrieved 03/04/2015. Check date values in: ,access-date= (help) "Healthy Kids Association ... Data also proposed a decrease in weight gain as a result of increased consumption lessens the risk of developing diabetes type ... A diet rich with Calcium, Vitamin C, B Vitamins, Iodine and Zinc ensures a growing child receives the most benefits from the ...
Epithelial sodium channel blockers: amiloride and triamterene.. Calcium-sparing diureticsEdit. The term "calcium-sparing ... TypesEdit. High ceiling/loop diureticEdit. High ceiling diuretics may cause a substantial diuresis - up to 20%[3] of the ... The reduced concentration of calcium in the urine can lead to an increased rate of calcium in serum. The sparing effect on ... calcium chloride, ammonium chloride 1. Arginine vasopressin. receptor 2 antagonists amphotericin B, lithium[13][14]. Inhibits ...
Manufacturers do not state which particular type of capsaicinoids are used. Personal pepper sprays can range from a low of 0.18 ... because there are six different types of capsaicinoids, causing different levels of irritation. ... See also: Receptor/signaling modulators • Ion channel modulators. Retrieved from "https://en.wikipedia.org/w/index.php?title= ...
NMDA receptor activation by rapid successive firing allows calcium influx in addition to sodium. The calcium influx triggered ... Certain types of physical exercise have been shown to markedly (threefold) increase BDNF synthesis in the human brain, a ... will communicate regularly and maintain the synapse structure and function long after the initial activation of NMDA channels. ... Promoter IV activity, leading to the translation of exon IV-containing mRNA, is strongly stimulated by calcium and is primarily ...
TypesEdit. There are three types of dentin, primary, secondary and tertiary.[13][14] Secondary dentin is a layer of dentin ... It is made up of 70% inorganic materials (mainly hydroxylapatite and some non-crystalline amorphous calcium phosphate), 20% ... Dentine consists of microscopic channels, called dentinal tubules, which radiate outward through the dentine from the pulp to ... It is of two types, either reactionary, where dentin is formed from a pre-existing odontoblast, or reparative, where newly ...
Inhibition of voltage-gated sodium channels and voltage-gated calcium channels (by kavain and methysticin). ... acetone in the two types of preparations) is responsible for the difference in toxicity as extraction of glutathione in ... due to an idiosyncratic reaction of the metabolic type",[77] "liver injury by kava is basically a preventable disease".[78] In ... While some bars have been committed to only serving the traditional forms and types of kava, other establishments have been ...
Calcium concentrations falling below the needs of some freshwater organisms. *The additive-and possibly synergistic-effects of ... which underlies many larger rivers and can contain substantially more water than is seen in the open channel. It may also be in ... are types of freshwater systems. ...
Ion channel. modulators. Calcium blockers. *Gabapentin. *Gabapentin enacarbil. *Mirogabalin. *Pregabalin. *Ziconotide. Sodium ...
... calcium channel blockers) ବା ବିଟା ବ୍ଲକର (beta blockers) ଦିଆଯାଏ । ଦୀର୍ଘକାଳୀନ ଭିତ୍ତିରେ କେତେକ ଲୋକଙ୍କର ଆସ୍ପିରିନ (aspirin) ବା ... "Types of Arrhythmia". NHLBI. July 1, 2011.. .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output .citation q{ ...
L-Type calcium channel blockers (e.g., dihydropyridines: nifedipine). *Nebivolol (beta blocker) ... Similarly, pentamidine inhibits type II topoisomerase in the mitochondria of the Trypanosoma parasite, resulting in a broken ... "Structural insights into calcium-bound S100P and the V domain of the RAGE complex". PLOS ONE. 9 (8): e103947. Bibcode ...
Varying amounts of potassium, sodium, phosphorus, calcium, magnesium, iron, and zinc were present.[81] ... reported that in Arabia locusts were eaten frequently and one Arab described to a European traveler the different types of ... Visual neuron of the locust, Ri Channel video, October 2011. *FAO Locust Watch ...
This type of fracture occurs only in very homogeneous minerals. Other types of fracture are fibrous, splintery, and hackly. The ... In a limestone, calcite or aragonite (both CaCO3) form because the rock is rich in calcium and carbonate. A corollary is that a ... They form in the presence of water at low temperatures and pressures, and have channels and voids in their structure. Zeolites ... These rocks may consist of one type of mineral, or may be an aggregate of two or more different types of minerals, spacially ...
These holes are proteins that are called calcium channels. The calcium ions rush into the cell. Calcium also comes out of a ... Types of muscles[change , change source]. There are three kinds of muscles: *Skeletal muscle, the muscle attached to bones. ... This calcium sticks to the specialized proteins actin and myosin. This triggers these proteins to contract the muscle. ...
... but could relate to actions of the drug on voltage-activated calcium channels. Lamotrigine blocks T-type calcium channels ... It also blocks L-, N-, and P-type calcium channels and has weak 5-hydroxytryptamine-3 (5-HT3) receptor inhibition. These ... However, it does inhibit native and recombinant high-voltage-activated calcium channels (N- and P/Q/R-types) at therapeutic ... Whether this activity on calcium channels accounts for lamotrigine's broader clinical spectrum of activity in comparison with ...
regulation of intracellular calcium activated chloride channel activity. • negative regulation of dendritic spine maintenance. ... type 5 metabotropic glutamate receptor binding. • type 8 metabotropic glutamate receptor binding. • signaling receptor activity ... calcium-mediated signaling using intracellular calcium source. • negative regulation of catalytic activity. • positive ... ion channel binding. • microtubule binding. • ATP-dependent protein binding. • metal ion binding. • tubulin binding. • protein ...
General: β-receptor blockers ("beta blockers"), calcium channel blockers, diuretics, cardiac glycosides, antiarrhythmics, ... Types of medicinesEdit. For the digestive systemEdit. *Upper digestive tract: antacids, reflux suppressants, antiflatulents, ... calcium channel blockers, thiazide diuretics, loop diuretics, aldosterone inhibitors. *Coagulation: anticoagulants, heparin, ...
Calcium channel blockers. *renin-angiotensin system *ACE inhibitors. *Angiotensin II receptor antagonists ... Types[edit]. *5-HT3 receptor antagonists block serotonin receptors in the central nervous system and gastrointestinal tract. As ... cation uptake by the receptor channel and contraction of isolated guinea-pig ileum", Eur J Pharmacol, 530 (1-2): 136-43, doi: ...
Calcium channel blockers are a common type of medication for high blood pressure and heart conditions. We discuss how these ... What is a calcium channel blocker?. Share on Pinterest. A doctor may prescribe calcium channel blockers to treat high blood ... Types and examples. There are two different types of calcium channel blocker, which are called dihydropyridines and ... Calcium channel blockers are a type of medication that people take to increase the flow of blood and oxygen to the heart. ...
T-type calcium channels in burst-firing, network synchrony, and epilepsy.. Cain SM1, Snutch TP. ... In this review we summarize recent findings concerning the role of T-type calcium channels in burst-firing and discuss how they ... Low voltage-activated (LVA) T-type calcium channels are well regarded as a key mechanism underlying the generation of neuronal ... Publication types, MeSH terms, Substances, Grant support. Publication types. *Research Support, Non-U.S. Govt ...
Calcium channel blockers are drugs used to lower blood pressure. Learn more from WebMD about how they work and their side ... certain drugs may interact with calcium channel blockers.. How Should I Take Calcium Channel Blockers?. Most calcium channel ... Interactions With Calcium Channel Blockers Calcium channel blockers are drugs used to lower blood pressure. They work by ... Side Effects of Calcium Channel Blockers. Potential side effects from taking a calcium channel blocker include:. * Dizziness or ...
... which inhibits the T-type calcium channel Cav3.2. This calcium channel was highly expressed in human GBM specimens and enriched ... Targetable T-type Calcium Channels Drive Glioblastoma. Ying Zhang, Nichola Cruickshanks, Fang Yuan, Baomin Wang, Mary Pahuski, ... Targetable T-type Calcium Channels Drive Glioblastoma. Ying Zhang, Nichola Cruickshanks, Fang Yuan, Baomin Wang, Mary Pahuski, ... Targetable T-type Calcium Channels Drive Glioblastoma. Ying Zhang, Nichola Cruickshanks, Fang Yuan, Baomin Wang, Mary Pahuski, ...
... were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or Cav2.2 channel ... Keywords: N-type calcium channel; Cav2.2; channel blocker; pain; FLIPR N-type calcium channel; Cav2.2; channel blocker; pain; ... were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or Cav2.2 channel ... Inhibition of N-Type Calcium Channels by Fluorophenoxyanilide Derivatives. Ellen C. Gleeson 1,2. ...
Mus musculus calcium channel, voltage-dependent, T type, alpha 1G subunit (Cacna... Mus musculus calcium channel, voltage- ... Mus musculus calcium channel, voltage-dependent, T type, alpha 1G subunit (Cacna1g), transcript variant 3, mRNA. NCBI Reference ... See the reference protein sequence for voltage-dependent T-type calcium channel subunit alpha-1G isoform c (NP_001171359.1). ... Calcium Regulation in the Cardiac Cell Calcium Regulation in the Cardiac CellCalcium is a common signaling mechanism, as once ...
Voltage-dependent calcium channel, L-type, alpha-1 subunit (IPR005446) *Voltage-dependent calcium channel, L-type, alpha-1S ... while the Cav3 family mediates T-type calcium currents.. L-type calcium channels are formed from alpha-1S, alpha-1C, alpha-1D, ... The Cav1 family forms channels mediating L-type calcium currents, the Cav2 family mediates P/Q-, N-, and R-type calcium ... Nomenclature of voltage-gated calcium channels.. Neuron 25 533-5 2000. Triggle DJ. 1,4-Dihydropyridines as calcium channel ...
R type, alpha 1E subunit Identifiers Symbol CACNA1E Alt. Symbols CACNL1A6 Entrez 777 HUGO 1392 OMIM ... R-type calcium channel calcium channel, voltage-dependent, ... Calcium channel. Voltage-dependent calcium channel (L-type/Cavα ... The R-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α1 subunit is the ... 1.1, 1.2, 1.3, 1.4), N-type, P-type/Cavα(2.1), Q-type, R-type, T-type, β-subunits (β1, β2, β4), γ-subunits (γ2) • Inositol ...
2011) Location of release sites and calcium-activated chloride channels relative to calcium channels at the photoreceptor ... Lateral Mobility of Presynaptic L-Type Calcium Channels at Photoreceptor Ribbon Synapses. Aaron J. Mercer, Minghui Chen and ... 2004) Role of lipid microdomains in P/Q-type calcium channel (Cav2.1) clustering and function in presynaptic membranes. J Biol ... 2004) The CACNA1F gene encodes an L-type calcium channel with unique biophysical properties and tissue distribution. J Neurosci ...
... the possible role of auxiliary subunit composition of the channels in Angiotensin II modulation of L-type calcium channels has ... Angiotensin II regulation of L-type calcium currents in cardiac muscle is controversial and the underlying signaling events are ... L-type calcium channel β subunit modulates angiotensin II responses in cardiomyocytes Channels (Austin). May-Jun 2011;5(3):280- ... the possible role of auxiliary subunit composition of the channels in Angiotensin II modulation of L-type calcium channels has ...
T-Type Calcium Channel Blocker, for the Treatment of Pain Experimental Clinical Study Expected to Initiate Third Quarter 2013 ... About Z944 and T-type Calcium Channel Blockers. Z944 is a novel, oral, state-dependent, selective T-type calcium channel ... Zalicus Advancing Clinical Development of Z944, Its Novel, Oral, T-Type Calcium Channel Blocker, for the Treatment of Pain ... T-type calcium channels are known to be widely implicated in the frequency and intensity of pain signals, and we believe Z944 ...
... and R-type Ca2+ channels are replaced by P/Q-type Ca2+ channels with development. In contrast, multiple types of Ca2+ channels ... 1991) N-type and L-type calcium channels are present in nerve growth cones. Numbers increase on synaptogenesis. Dev Brain Res ... Using type-specific Ca2+ channel blocker toxins, we have demonstrated that the contributions of N-type Ca2+ channels to ... Among them, the ω-conotoxin GVIA-sensitive N-type channels and the ω-Aga-IVA-sensitive P/Q-type channels mediate fast synaptic ...
Abstract 16089: Functional Coupling of SK Channels and L-type Calcium Channels in Cardiomyocytes. Xiao-Dong Zhang, Wei Chun ... Abstract 16089: Functional Coupling of SK Channels and L-type Calcium Channels in Cardiomyocytes ... Abstract 16089: Functional Coupling of SK Channels and L-type Calcium Channels in Cardiomyocytes ... Abstract 16089: Functional Coupling of SK Channels and L-type Calcium Channels in Cardiomyocytes ...
Voltage-dependent L-type calcium channel subunit alpha-1C. Q13936. Details. Voltage-dependent L-type calcium channel subunit ... Voltage-dependent L-type calcium channel subunit alpha-1F. O60840. Details. Voltage-dependent L-type calcium channel subunit ... Voltage-dependent L-type calcium channel subunit beta-1. Q02641. Details. Voltage-dependent L-type calcium channel subunit beta ... Voltage-dependent L-type calcium channel subunit beta-3. P54284. Details. Voltage-dependent L-type calcium channel subunit beta ...
Calcium signalling through L-type calcium channels: role in pathophysiology of spinal nociceptive transmission, British Journal ... L-type calcium channels and NMDA receptors: a determinant duo for short-term nociceptive plasticity. Authors. *. Pascal Fossat, ... Shohei Yamamoto, Yuma Suzuki, Hideki Ono, Kazuhiko Kume, Masahiro Ohsawa, N- and L-type calcium channels blocker cilnidipine ... Cav1.2 and Cav1.3 L-type calcium channels independently control short- and long-term sensitization to pain, The Journal of ...
T-type Cav3.1 channels augment nitric oxide and co-localize with eNOS. Therefore, the hypothesis... ... T-type Cav3.1 channels augment nitric oxide and co-localize with eNOS. Therefore, the hypothesis was that T-type channels ... and T-type calcium channels in local and remote calcium responses in rat mesenteric terminal arterioles. J Vasc Res 46:138-151 ... Deletion of T-type calcium channels Cav3.1 or Cav3.2 attenuates endothelial dysfunction in aging mice. ...
アルコール長期曝露によるL型高電位開口性カルシウムチャネルの機能変化とその意義 [in Japanese] Functional significance of L-type high voltage-gated calcium channels ... Protein kinase Cε mediates up-regulation of N-type calcium channels by ethanol MCMAHON T. ... Functional changes of L-type high voltage-gated calcium channels (HVCCs) after sustained exposure of cerebral cortical neurons ... Subunits of purified calcium channels α2 and δ are encoded by
2. The channel had a conductance of 210 pS in a 150 mM:150 mM K+ gradient, was highly selective for K+ ov … ... A high-conductance calcium-activated potassium channel (BK KCa) was characterized at a cholinergic presynaptic nerve terminal ... Single-channel properties of BK-type calcium-activated potassium channels at a cholinergic presynaptic nerve terminal J Physiol ... suggesting that the channel can be activated by calcium ion influx through neighbouring calcium channels. 5. The properties of ...
Reducing agents sensitize C-type nociceptors by relieving high-affinity zinc inhibition of T-type calcium channels J Neurosci ... New evidence that both T-type calcium channels and GABAA channels are responsible for the potent peripheral analgesic effects ... Recent studies have highlighted the importance of T-type calcium channels (T-channels) in peripheral nociception; therefore, ... Silencing of the Cav3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception EMBO J 2005; ...
Two types of calcium channels in single smooth muscle cells from rabbit ear artery studies with whole-cell and single-channel ... Single L-Type Calcium Channels in Smooth Muscle Cells From Resistance Arteries of Spontaneously Hypertensive Rats. Yusuke Ohya ... which inactivated the T-type Ca2+ channels as well as Na+ channels10; and (3) the channel opening disappeared with the ... Single-channel conductance of L-type Ca2+ channels was about 20 pS in both SHR and WKY. We used 50 mmol/L Ba2+ to record the ...
The R-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α1 subunit forms ... "Entrez Gene: CACNA1E calcium channel, voltage-dependent, R type, alpha 1E subunit". Soong TW, Stea A, Hodson CD, Dubel SJ, ... This α1 subunit is also known as the calcium channel, voltage-dependent, R type, alpha 1E subunit (CACNA1E) or Cav2.3 which in ... They are poorly understood, but like Q-type calcium channels, they appear to be present in cerebellar granule cells. They have ...
Long-Lasting calcium channels). The new T-type channels were much different from the L-type calcium channels due to their ... Calcium channel blockers (CCB) such as mibefradil can also block L-type calcium channels, other enzymes, as well as other ... Novel T-type calcium channel inhibitors have recently been discovered which more selectively target the CaV3.3 channel sub-type ... The α1 subunit also determines the type of calcium channel. The β, α2δ, and γ subunits, present in only some types of calcium ...
... Minerva ... Estradiol receptor antagonist reduces ventricular arrhythmia via L-type calcium channels in chronic heart failure.. *. ... Estradiol receptor antagonist reduces ventricular arrhythmia via L-type calcium channels in chronic heart failure. Minerva ... Exendin-4 Reduces Ventricular Arrhythmia Activity and Calcium Sparks-Mediated Sarcoplasmic Reticulum Ca Leak in Rats with Heart ...
Reducing Agents Sensitize C-Type Nociceptors by Relieving High-Affinity Zinc Inhibition of T-Type Calcium Channels. Michael T. ... Reducing Agents Sensitize C-Type Nociceptors by Relieving High-Affinity Zinc Inhibition of T-Type Calcium Channels ... Reducing Agents Sensitize C-Type Nociceptors by Relieving High-Affinity Zinc Inhibition of T-Type Calcium Channels ... Reducing Agents Sensitize C-Type Nociceptors by Relieving High-Affinity Zinc Inhibition of T-Type Calcium Channels ...
The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the high-voltage activated (HVA ... Voltage-dependent N-type calcium channel subunit alpha-1B - O55017 (CAC1B_MOUSE) ... Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a ... In many cases, this subunit is sufficient to generate voltage-sensitive calcium channel activity. The auxiliary subunits beta ...
Voltage-dependent calcium channel type A subunit alpha-1 - P91645 (CAC1A_DROME) ... Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a ... variety of calcium-dependent processes, including muscle contraction, neurotransmitter release, gene expression, cell motility ...
Voltage-dependent L-type calcium channel subunit alpha-1D. Details. Name. Voltage-dependent L-type calcium channel subunit ... Voltage-dependent L-type calcium channel subunit alpha-1D. Q01668. Details. Drug Relations. Drug Relations. DrugBank ID. Name. ...
The isoform alpha-1E gives rise to R-type calcium currents. ... mediate the entry of calcium ions into excitable cells and are ... also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, ... Voltage-dependent R-type calcium channel subunit alpha-1E (Brain calcium channel II, BII) (Calcium channel, L type, alpha-1 ... Voltage-dependent R-type calcium channel subunit alphaUniRule annotation. Automatic assertion according to rulesi ...
T-type calcium channels are key contributors to neuronal physiology where they shape electrical activity of nerve cells and ... Senatore A & Spafford JD (2015). Physiology and pathology of voltage-gated T-type calcium channels. In T-type Calcium Channels ... Calcium channel T-type channel Cav3.2 Glucose N-glycosylation Trafficking ... Modulation of Cav3.2 T-type calcium channel permeability by asparagine-linked glycosylation. Channels (Austin) 10(3):175-184 ...
Proliferation of GSCs reportedly requires calcium influx through T-type calcium channels (Cav3.2). In this study we ... Abstract 3147: Comprehensive characterization of the role of T-type calcium channels in glioblastoma. Ying Zhang, Nichola ... Comprehensive characterization of the role of T-type calcium channels in glioblastoma [abstract]. In: Proceedings of the ... Abstract 3147: Comprehensive characterization of the role of T-type calcium channels in glioblastoma ...
  • The Cav1 family forms channels mediating L-type calcium currents, the Cav2 family mediates P/Q-, N-, and R-type calcium currents, while the Cav3 family mediates T-type calcium currents. (ebi.ac.uk)
  • Angiotensin II regulation of L-type calcium currents in cardiac muscle is controversial and the underlying signaling events are not completely understood. (nih.gov)
  • In fact, Ca 2+ currents directly recorded from the auditory calyceal presynaptic terminal were identified as N-, P/Q-, and R-types at postnatal day 7 (P7) to P10 but became predominantly P/Q-type at P13. (jneurosci.org)
  • SK currents coupled with Ca 2+ influx via LTCCs continued to be elicited after application of caffeine, ryanodine or thapsigargin to deplete SR Ca 2+ store, suggesting that LTCCs provide the immediate Ca 2+ microdomain for the activation of SK channels in CMs. (ahajournals.org)
  • BAY K 8644 (10(-8)-10(-4) M) produced a dose-dependent stimulation in CCK release with a mean effective concentration value of 0.2 mu M Recordings of single-channel currents from inside-out membrane patches showed activation of calcium channels by BAY K 8644 (1 mu M), with a primary channel conductance of 26.0 +/- 1.2 pS. (rti.org)
  • These disturbances were accompanied by significant biophysical and biochemical modulation of T-channels in dorsal root ganglion neurons as measured by a large increase in the amplitude of T-currents and the expression of mRNA. (diabetesjournals.org)
  • The T-type channel is regulated by both dopamine and other neurotransmitters, which inhibit T-type currents. (wikipedia.org)
  • To further test the hypothesis that activation of L-type Ca 2+ channels in arterial smooth muscle cells would be enhanced in SHR, we recorded single Ca 2+ channel currents in resistance mesenteric artery cells from SHR and WKY (8 to 9 weeks of age) using a cell-attached patch clamp technique. (ahajournals.org)
  • The amplitude of whole-cell L-type Ca 2+ channel currents is increased in resistance mesenteric arteries of young SHR, in cerebral arteries of adult stroke-prone SHR, and in azygous vein of neonatal SHR compared with age-matched WKY. (ahajournals.org)
  • Here, we demonstrate that reducing agents as well as endogenous metal chelators sensitize C-type dorsal root ganglion nociceptors by chelating Zn 2+ ions off specific extracellular histidine residues on Ca v 3.2 T-channels, thus relieving tonic channel inhibition, enhancing Ca v 3.2 currents, and lowering the threshold for nociceptor excitability in vitro and in vivo . (jneurosci.org)
  • Here, we show that reducing agents selectively sensitize C-type nociceptors that express Ca v 3.2 T-currents. (jneurosci.org)
  • The isoform alpha-1B gives rise to N-type calcium currents. (rcsb.org)
  • Recently, it was demonstrated that asparagine-linked glycosylation not only plays an essential role in regulating cell surface expression of Ca v 3.2 channels, but may also support glucose-dependent potentiation of T-type currents. (springer.com)
  • The authors of this paper studied the effect of PnTx3-6 on a panel of recombinant Ca channels and on Ca channel currents recorded from neuroblastoma cells. (pharmiweb.com)
  • In contrast, DB1, DB6 and midget bipolar cells lacked T-type currents. (arvojournals.org)
  • one type, which we denote as DB3a, expressed large voltage-gated sodium currents but lacked T-type calcium currents, while a second type, which we denote as DB3b, exhibited large T-type calcium currents but lacked sodium currents. (arvojournals.org)
  • T-type currents remained in cells in which the axon terminal system had been removed, suggesting localization of channels in the somatic and/or dendritic compartments. (arvojournals.org)
  • Immunohistochemistry for the T-type calcium channel subunit, CaV3.1, revealed expression in the somatodendritic compartment of the same bipolar cell types that exhibited T-type currents by electrophysiology. (arvojournals.org)
  • These data demonstrate the presence of CaV3.1-mediated currents in sub-types of primate bipolar cells. (arvojournals.org)
  • Comparing the isolated T-type calcium currents in cells with and without processes revealed that cells with dendrites had much larger T-type currents than soma-only cells and we concluded that the dendrites had 4 to 12 times the channel density as that observed in the soma. (arvojournals.org)
  • Voltage-clamp data were used to construct a model of the T-type currents and this model was used to study the roles which T-type calcium channels can play in contributing to ganglion cell function. (arvojournals.org)
  • A diverse set of calcium channels contribute to the timely regulation of calcium currents at cellular level. (nc3rs.org.uk)
  • Myocytes isolated from the RV of pulmonary hypertensive rats that displayed elevated T-type currents and RV dysfunction, also showed impaired contractility with decreased sensitivity to Ca 2+ . (ahajournals.org)
  • The cells displayed typical high-voltage activated calcium currents sensitive to the L-type Ca v blocker calciseptine. (ahajournals.org)
  • Cardiac myocytes express two types of voltage operated calcium currents, a high voltage activated (HVA) L-type, and a low voltage activated (LVA) T-type. (illinois.edu)
  • Several subtypes of voltage-gated Ca2+ channels are known and the L-type has been found to be the main contributor to electrical Ca2+ currents in beta-cells. (avhandlingar.se)
  • The cell line was pharmacologically characterized by ion channel specific modulators, and revealed functional P/Q-type calcium currents. (eurekaselect.com)
  • The T-type channels generate currents that are both transient, owing to fast inactivation, and tiny, owing to small conductance. (nih.gov)
  • Moreover, upon switching to divalent free external solutions, Orai3 currents were considerably more stable than Orai1 or Orai2, indicating that Orai3 channels undergo a lesser degree of depotentiation. (unboundmedicine.com)
  • Calcium channel blockers are a type of medication that people take to increase the flow of blood and oxygen to the heart. (medicalnewstoday.com)
  • Calcium channel blockers are common medications that have a low risk of complications. (medicalnewstoday.com)
  • Calcium channel blockers reduce the amount of calcium that can enter muscle cells in the heart and blood vessel walls via these channels. (medicalnewstoday.com)
  • Doctors commonly use calcium channel blockers to treat high blood pressure . (medicalnewstoday.com)
  • Scientists are currently exploring other potential uses for calcium channel blockers. (medicalnewstoday.com)
  • For example, by reducing high blood pressure, they believe that calcium channel blockers may be able to lower the risk of Alzheimer's disease . (medicalnewstoday.com)
  • Several other types of medication have an effect similar to that of calcium channel blockers. (medicalnewstoday.com)
  • Researchers have found that both beta-blockers and calcium channel blockers are effective in lowering blood pressure, making them useful treatments for a variety of conditions that affect the heart, including angina and arrhythmia. (medicalnewstoday.com)
  • However, the American Heart Association recommend calcium channel blockers as a first-line pharmacological treatment for high blood pressure in most people and advise that beta-blockers should be a second-choice option. (medicalnewstoday.com)
  • Doctors may also minimize this risk by prescribing extended release calcium channel blockers. (medicalnewstoday.com)
  • Calcium channel blockers are drugs used to lower blood pressure . (webmd.com)
  • certain drugs may interact with calcium channel blockers. (webmd.com)
  • How Should I Take Calcium Channel Blockers? (webmd.com)
  • Grapefruits and grapefruit juice can affect the action of many of the calcium channel blockers. (webmd.com)
  • We have addressed this question by testing type-specific Ca 2+ channel blockers at developing central synapses. (jneurosci.org)
  • We showed that windup of the reflex is actually suppressed by blockers of L -type calcium current and Ca 2+ -activated non-specific cationic current (I can ), the two main depolarizing conductances of plateau potentials. (wiley.com)
  • Advances in the development of Cav2.2 (N-type) calcium channel blockers as analgesics. (pharmiweb.com)
  • Ca channel blockers stepped into the spotlight at the end of last year with the FDA approval of Elan's Ziconotide (PRIALT), an intrathecally administered peptide that blocks the Cav2.2 (N-type) channel. (pharmiweb.com)
  • Voltage-Dependent T-Type Calcium Channel Blockers - Pipeline Insight, 2019" offers comprehensive insights of the pipeline (under development) therapeutics scenario and growth prospects across "Voltage-Dependent T-Type Calcium Channel Blockers development. (reportbuyer.com)
  • Descriptive coverage of pipeline development activities for "Voltage-Dependent T-Type Calcium Channel Blockers - Pipeline therapeutics development coverage provides descriptive product profiles including (but not limited to) drug description, product development and R&D activities encompassing clinical and pre-clinical studies, designations, collaborations, licensing deals, grants, technologies and patent details. (reportbuyer.com)
  • The report assesses the active Voltage-Dependent T-Type Calcium Channel Blockers pipeline products by developmental stage, product type, molecule type, and administration route. (reportbuyer.com)
  • Membrane depolarization of neurons to −30 mV leads to a sustained increase in CREB phosphorylation that is eliminated by dihydropyridine (DHP) LTC blockers, but is only slightly sensitive to blockers of N -methyl- d -aspartate (NMDA) receptors and is completely insensitive to blockers of other voltage-gated calcium channels ( Fig. 1 A) ( 9 ). (sciencemag.org)
  • 2,3 However, the inability of depolarization to change calcium concentration in JG cells and the lack of effect of calcium channel blockers on renin release have questioned the relevance of Ca v in the control of renin secretion. (ahajournals.org)
  • Both angiotensin II type I receptor blockers (ARBs) and calcium channel blockers (CCBs) are widely used antihypertensive drugs. (springermedizin.de)
  • P/Q-channel blockers may normalize current flow and consequently lead to an alleviation of disease symptoms. (eurekaselect.com)
  • Here we describe a high throughput screen (HTS) for P/Q-type calcium channel blockers and the confirmation of hits by automated electrophysiology. (eurekaselect.com)
  • The discovery of P/Q-channel blockers may foster the development of new therapeutics for a variety of neurological diseases. (eurekaselect.com)
  • Calcium channel blockers, also referred to as calcium antagonists, can be used to treat several different medical conditions. (healthguideinfo.com)
  • Like all medications, calcium channel blockers can cause side effects. (healthguideinfo.com)
  • 2009). Calcium Channel Blockers. (healthguideinfo.com)
  • What are calcium channel blockers (CCBs) and how do they work? (rxlist.com)
  • Calcium channel blockers are drugs that block the entry of calcium into the muscle cells of the heart and arteries. (rxlist.com)
  • Thus, by blocking the entry of calcium, calcium channel blockers reduce electrical conduction within the heart, decrease the force of contraction (work) of the muscle cells, and dilate arteries. (rxlist.com)
  • In addition, calcium channel blockers slow electrical conduction through the heart and thereby correct abnormal rapid heartbeats. (rxlist.com)
  • For what conditions are calcium channel blockers used? (rxlist.com)
  • Are there any differences among calcium channel blockers? (rxlist.com)
  • Although calcium channel blockers have a similar mechanism of action, they differ in their ability to affect heart muscle vs. arteries, and they differ in their ability to affect heart rate and contraction. (rxlist.com)
  • Sexual dysfunction , overgrowth of gums, and liver dysfunction also have been associated with calcium channel blockers. (rxlist.com)
  • With which drugs do calcium channel blockers interact? (rxlist.com)
  • Several calcium channel blockers [for example, diltiazem (Cardizem LA, Tiazac), felodipine ( Plendil )] increase the level of cyclosporine ( Sandimmune , Neoral , Restasis ) and similarly lead to toxicity of cyclosporine. (rxlist.com)
  • What are some examples of calcium channel blockers available? (rxlist.com)
  • A set of fluorophenoxyanilides, designed to be simplified analogues of previously reported ω-conotoxin GVIA mimetics, were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. (mdpi.com)
  • In cardiomyocytes, Angiotensin II exposure induces rapid inhibition of L-type current with a magnitude that is correlated with the rate of current inactivation. (nih.gov)
  • Over-expression of individual b subunits in heterologous systems reveals that the magnitude of Angiotensin II inhibition is dependent on the Ca(v)β subunit isoform, with Ca(v)β(1b) containing channels being more strongly regulated. (nih.gov)
  • Moreover, PLC or diacylglycerol lipase inhibition prevents the Angiotensin II effect on L-type calcium channels, while PKC inhibition with chelerythrine does not, suggesting a role of arachidonic acid in this process. (nih.gov)
  • These data demonstrate that Ca(v)β subunits alter the magnitude of inhibition of L-type current by Angiotensin II. (nih.gov)
  • It is concluded that inhibition of potassium channel activity depolarizes the plasma membrane, thereby activating L-type, but not T-type, calcium channels. (rti.org)
  • We then demonstrate that the sensitization is facilitated through a novel mechanism, whereby reducing agents chelate Zn 2+ ions off specific extracellular histidine residues in domain I of Ca v 3.2, thereby relieving tonic channel inhibition. (jneurosci.org)
  • Ca v 1.3 channels were less sensitive to pentobarbital inhibition than Ca v 1.2 channels, similar to dihydropyridine (DHP) L-VGCC antagonists. (aspetjournals.org)
  • Compared with Ca v 1.2, recombinant Ca v 1.3 channels were 1.5-fold less sensitive to inhibition by flurazepam, 3-fold less sensitive to inhibition by pentobarbital, and 3-fold more sensitive to inhibition by diltiazem. (aspetjournals.org)
  • The n5209 suppressor of peptidergic inhibition affects the T-type calcium channel gene cca-1 . (elifesciences.org)
  • Inhibition of K V channels with 4-AP inhibited 21% of the current. (ahajournals.org)
  • Our results suggest that NNC55-0396 could be a more favorable T-type Ca 2+ antagonist than its parent compound, mibefradil, which was withdrawn from the market because of strong inhibition of CYP3A4. (aspetjournals.org)
  • Fujita T, Ando K, Nishimura H, Ideura T, Yasuda G, Isshiki M, Takahashi K, Cilnidipine versus Amlodipine Randomised Trial for Evaluation in Renal Disease (CARTER) Study Investigators: Antiproteinuric effect of the calcium channel blocker cilnidipine added to renin-angiotensin inhibition in hypertensive patients with chronic renal disease. (springermedizin.de)
  • Inhibition of TRPC 3 attenuates vascular calcium influx in spontaneously hypertensive rats ( SHR s). (ahajournals.org)
  • Activation of several G-protein-coupled receptors leads to voltage- dependent (VD) inhibition of N- and P/Q-type Ca 2+ channels via G-protein βγ subunits (Gβγ). (elsevier.com)
  • The purpose of the present study was to determine the ability of different Gβγ combinations to produce VD inhibition of N-type Ca 2+ channels in rat superior cervical ganglion neurons. (elsevier.com)
  • Various Gβγ combinations were heterologously overexpressed by intranuclear microinjection of cDNA and tonic VD Ca 2+ channel inhibition evaluated using the whole-cell voltage-clamp technique. (elsevier.com)
  • Overexpression of Gβ1-Gβ5, in combination with several different Gγ subunits, resulted in tonic VD Ca 2+ channel inhibition. (elsevier.com)
  • Inhibition of the activation pathway of the T-type calcium channel Ca(V)3.1 by ProTxII. (uchicago.edu)
  • The molecular basis for T-type Ca2+ channel inhibition by G protein beta2gamma2 subunits. (uchicago.edu)
  • 1,4-dihydropyridines act as antagonists of these channels [ PMID: 12825828 , PMID: 15336981 ]. (ebi.ac.uk)
  • CONCLUSIONS: These data suggest that T-type calcium channel antagonists have potential for alleviating nicotine addiction by selectively decreasing the incentive motivational properties of nicotine. (biomedsearch.com)
  • Background and Purpose Neuroprotection by antagonists of both L-type and N-type calcium channels occurs in in vivo models of ischemia. (ahajournals.org)
  • The site of action of calcium channel antagonists is unclear, however, and it is likely that a combination of vascular and direct neuronal actions occurs. (ahajournals.org)
  • Conclusions These studies present clear evidence that neuroprotection by selective N-type calcium channel antagonists is mediated directly through neuronal calcium channels. (ahajournals.org)
  • 10 11 12 Such contradictory results could be explained if the effects of calcium channel antagonists are all mediated by effects on blood flow in vivo, or it may be that in dissociated cell cultures subjected to oxygen-glucose deprivation, cell death occurs through pathways where voltage-gated calcium channels are relatively less important than in vivo. (ahajournals.org)
  • Uchida S, Yamada S, Nagai K, Deguchi Y, Kimura R (1997) Brain pharmacokinetics and in vivo receptor binding of 1, 4-dihydropyridine calcium channel antagonists. (springer.com)
  • Swart T, Hurley MJ (2016) Calcium channel antagonists as disease-modifying therapy for Parkinson's disease: therapeutic rationale and current status. (springer.com)
  • During the past three decades, Ca 2+ channel antagonists belonging to many structurally diverse classes, such as dihydropyridines, phenylalkylamines, and benzothiazepines, have been developed for the treatment of hypertension and chronic stable angina pectoris ( Oparil and Calhoun, 1991 ). (aspetjournals.org)
  • Calcium antagonists: Do they equally protect against kidney injury? (uchicago.edu)
  • The calcium channel antagonists (CCAs) are commonly used in the therapy of various cardiovascular diseases and are under investigation due to their potential in modulating calcium-dependent neurotransmitter release. (unboundmedicine.com)
  • The opening and closing of these channels by depolarizing stimuli, such as action potentials, allows Ca2+ ions to enter neurons down a steep electrochemical gradient, producing transient intracellular Ca2+ signals. (ebi.ac.uk)
  • As a member of the Cav3 subfamily of voltage-gated calcium channels, the function of the T-type channel is important for the repetitive firing of action potentials in cells with rhythmic firing patterns such as cardiac muscle cells and neurons in the thalamus of the brain. (wikipedia.org)
  • Recent studies have demonstrated an important role for T-type Ca 2+ channels (T-channels) in controlling the excitability of peripheral pain-sensing neurons (nociceptors). (jneurosci.org)
  • Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons. (rcsb.org)
  • Duzhyy DE, Viatchenko-Karpinski VY, Khomula EV, Voitenko NV, Belan PV (2015) Upregulation of T-type Ca2+ channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons. (springer.com)
  • T-type channels have been first well described functionally in primary sensory neurons ( Carbone and Lux, 1984 ). (frontiersin.org)
  • L-type calcium channels and MAP kinase contribute to thyrotropin-releasing hormone induced depolarization in thalamic paraventricular nucleus neurons. (physiology.org)
  • Collectively, the data imply that TRH-induced depolarization and inward current in PVT neurons involve both a dependency on extracellular Ca 2+ influx via opening of L-type Ca 2+ channels, a sensitivity of a TRPC-like component to intracellular Ca 2+ release via ryanodine channels, and a modulation by MAPK of a GIRK-like conductance component. (physiology.org)
  • Neurons express at least nine types of voltage-gated Ca 2+ channels that are specialized for different functions ( 2 ). (sciencemag.org)
  • The egg-laying circuit comprises three cell-types: the serotonergic HSNs, the cholinergic ventral cord neurons VC4 and VC5, and electrically coupled vulval and uterine muscles, of which the vulval muscles (VMs) receive direct synaptic input from motor neurons ( Figure 1-figure supplement 1 ). (elifesciences.org)
  • For many neurons, N-type calcium channels provide the primary pathway for calcium influx during an action potential. (rupress.org)
  • Studies on neonatal rat sympathetic neurons found that N-channels, like L-type calcium channels, could gate in different modes. (rupress.org)
  • This 48-amino acid peptide, omega-agatoxin (omega-Aga)-IVB, was found to be a potent (Kd, approximately 3 nM) blocker of P-type calcium channels in rat cerebellar Purkinje neurons but had no activity against T-type, L-type, or N-type calcium channels in a variety of neurons. (aspetjournals.org)
  • CACNA1E gives rise to R-type calcium channels that belong to the high-voltage activated (HVA) group, which may be involved in modulating firing patterns of neurons important for information processing. (thefreedictionary.com)
  • facilitate trafficking and targeting of the voltage-gated N-type Ca 2+ channel (Cav2.2) in neurons. (biologists.org)
  • In this study, we have used immunocytochemistry, immunoprecipitation, biotinylation, electrophysiology and a transmitter-release radioimmunoassay to demonstrate the effect(s) of CRMP-2 on Ca 2+ channel function and transmitter release in sensory neurons. (biologists.org)
  • Ciliary neurotrophic factor-treated astrocyte conditioned medium regulates the L-type calcium channel activity in rat cortical neurons. (nextbio.com)
  • β-Hydroxybutyrate modulates N-type calcium channels in rat sympathetic neurons by acting as an agonist for the G-protein-coupled receptor FFA3. (semanticscholar.org)
  • However, it is not known whether presynaptic N-type Ca 2+ channels contribute to short-term synaptic plasticity (STP) mediated by GABA release at inhibitory synapses of cultured hippocampal neurons. (begellhouse.com)
  • These results confirm that N-type Ca 2+ channels are highly involved in inhibitory synaptic transmission and short-term synaptic plasticity in cultured hippocampal neurons. (begellhouse.com)
  • T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. (nih.gov)
  • [7] [8] Blockade of N-type calcium channels in sensory neurons has therapeutic potential for the treatment of certain types of pain, particularly neuropathic pain. (ipfs.io)
  • The alpha-1 subunit forms the pore for the import of extracellular calcium ions and, though regulated by the other subunits, is primarily responsible for the pharmacological properties of the channel [ PMID: 11031246 ]. (ebi.ac.uk)
  • L-type calcium channels are formed from alpha-1S, alpha-1C, alpha-1D, and alpha-1F subunits. (ebi.ac.uk)
  • α 2 δ 4 antibodies labeled photoreceptor terminals and colocalized with antibodies to synaptic vesicle glycoprotein 2 and voltage-gated Ca 2+ channel 1.4 (Ca V 1.4) α 1 subunits. (jneurosci.org)
  • L-type Ca V channels are composed of a pore-forming α subunit, with accessory β, α 2 δ and γ subunits ( Catterall, 2000 ). (jneurosci.org)
  • In this work we study the role of Ca(v)β subunits and the intracellular signaling responsible for L-type calcium current modulation by Angiotensin II. (nih.gov)
  • 11 ) involving isoform-specific oligonucleotides that downregulate each of the three isoforms of pore-forming subunits of T-channel, Ca v 3.1 (α1G), Ca v 3.2 (α1H), and Ca v 3.3 (α1I), in DRG cells. (diabetesjournals.org)
  • The auxiliary subunits beta and alpha-2/delta linked by a disulfide bridge regulate the channel activity. (rcsb.org)
  • Dubel SJ, Altier C, Chaumont S, Lory P, Bourinet E, Nargeot J (2004) Plasma membrane expression of T-type calcium channel alpha(1) subunits is modulated by high voltage-activated auxiliary subunits. (springer.com)
  • By use of the whole-cell voltage-clamp technique, the current studies investigated the effects of BDZs (diazepam, flurazepam, and desalkylflurazepam), allopregnanolone, pentobarbital, and ethanol on recombinant L-VGCCs containing the neuronal L-type α 1 subunit, Ca v 1.2 or Ca v 1.3, along with β 3 and α 2 δ-1 subunits. (aspetjournals.org)
  • Antibodies to the three major classes of T-type calcium channel subunits (G,H,I) were developed and applied to the rat and tiger salamander retinas. (arvojournals.org)
  • The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. (biomol.com)
  • Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. (creativebiomart.net)
  • To this end, mutant Gβ subunits were constructed that differentially modulated N-type Ca 2+ and G-protein-gated inward rectifier K + channels. (elsevier.com)
  • Calcium channels are made up of subunits in various ratios, known by letters of the Greek alphabet (alpha, beta etc. (painonline.com)
  • Ball CJ, Wilson DP, Turner SP, Saint DA, Beltrame JF (2009) Heterogeneity of L- and T-channels in the vasculature: rationale for the efficacy of combined L- and T-blockade. (springer.com)
  • Blockade of potassium channels with barium chloride (5 mM) increased the release of CCK by 374.6 +/- 46.6% of control levels. (rti.org)
  • For example, it has been shown that pharmacological blockade of T-channels with mibefradil and ethosuximide ( 9 ), and with (3β,5α,17β)-17-hydroxyestrane-3-carbonitrile (ECN) ( 10 ), alleviates mechanical hypersensitivity induced by peripheral nerve injury in rats. (diabetesjournals.org)
  • Prior to impact, swine were randomly assigned to either calcium channel blockade with a verapamil infusion (0.4mg/kg) or placebo (normal saline, 100 ml) [11]. (thefreelibrary.com)
  • Blockade of Cav2.2 (N-type) channels has previously been shown to prevent pain transmission and activity against this channel has been proposed as the mechanism of action of Ziconotide, a neuroactive peptide developed by Elan as a novel non-opioid treatment for severe chronic pain. (pharmiweb.com)
  • TRH-induced inward current was unchanged by T-type Ca 2+ channel blockade, but was decreased by blockade of high-voltage-activated Ca 2+ channels (HVACCs). (physiology.org)
  • The aim of this project is to develop an Adverse Outcome Pathway (AOP) that describes the series of causally related key events triggered by the blockade of L-type calcium channel, and that can ultimately lead to heart failure. (nc3rs.org.uk)
  • 1 2 Removal of extracellular calcium has been demonstrated to prevent glutamate-induced neuronal death in such cultures, 3 4 5 and blockade of VSCCs by nifedipine reduces the damage that follows exposure to glutamate receptor agonists. (ahajournals.org)
  • 9 This is in contrast to data from in vivo studies in which there is clear evidence that blockade of either L-type or N-type calcium channels is neuroprotective. (ahajournals.org)
  • Blockade of K + channels with TEA inhibited 83% of the current at +105 mV. (ahajournals.org)
  • Blockade of calcium-sensitive voltage-gated K + channels (BK Ca ) with charybdotoxin or iberiotoxin inhibited 89% and 82% of the current, respectively. (ahajournals.org)
  • Mibefradil induces coronary and peripheral vasodilation through a direct effect on smooth muscle via blockade of T-type and L-type Ca 2+ channels ( Massie, 1997 ). (aspetjournals.org)
  • However, blockade of the RyRs also slightly improved spatial memory of the LPS-infused rats, demonstrating that other Ca +2 channels are dysregulated during chronic neuroinflammation. (biomedcentral.com)
  • Blockade of the N-type calcium channel is a potential therapeutic strategy for the treatment of alcoholism . (ipfs.io)
  • Their low threshold for activation combined with a rapid and transient calcium conductance generates low-threshold calcium potentials (LTCPs), upon the crest of which high frequency action potentials fire for a brief period. (nih.gov)
  • Voltage-gated calcium channels are classified as T, L, N, P, Q and R, and are distinguished by their sensitivity to pharmacological blocks, single-channel conductance kinetics, and voltage-dependence. (ebi.ac.uk)
  • Small conductance Ca 2+ -activated K + (SK) channels play significant roles in regulating the excitability of cardiomyocytes (CMs). (ahajournals.org)
  • 1. A high-conductance calcium-activated potassium channel (BK KCa) was characterized at a cholinergic presynaptic nerve terminal using the calyx synapse isolated from the chick ciliary ganglion. (nih.gov)
  • 2. The channel had a conductance of 210 pS in a 150 mM:150 mM K+ gradient, was highly selective for K+ over Na+, and was sensitive to block by external charybdotoxin or tetraethylammonium (TEA) and by internal Ba2+. (nih.gov)
  • There were no overt differences in conductance or [Ca2+]i sensitivity between BK channels from the transmitter release face and the non-release face. (nih.gov)
  • The new T-type channels were much different from the L-type calcium channels due to their ability to be activated by more negative membrane potentials, had small single channel conductance, and also were unresponsive to calcium antagonist drugs that were present. (wikipedia.org)
  • Single-channel conductance (20 pS) and open time (1 ms at 0 mV) did not differ in the two strains. (ahajournals.org)
  • 0 mV, have a slope conductance of ∼20 pS, a single channel current at 0 mV of 1.4 pA, and are active from a holding potential of −40 mV. (rupress.org)
  • Low voltage-activated (LVA) T-type calcium channels are well regarded as a key mechanism underlying the generation of neuronal burst-firing. (nih.gov)
  • Not only are T-type calcium channels known to be present within cardiac and smooth muscle, but they also are present in many neuronal cells within the central nervous system. (wikipedia.org)
  • T-type calcium channels are key contributors to neuronal physiology where they shape electrical activity of nerve cells and contribute to the release of neurotransmitters. (springer.com)
  • Voltage-activated Ca channels play a major role in many physiological processes including release of neurotransmitters and the regulation of neuronal excitability. (pharmiweb.com)
  • The Kelch-like 1 protein (KLHL1) is a neuronal actin-binding protein that modulates calcium channel function. (hindawi.com)
  • Benzodiazepines (BDZs) depress neuronal excitability via positive allosteric modulation of inhibitory GABA A receptors (GABA A R). BDZs and other positive GABA A R modulators, including barbiturates, ethanol, and neurosteroids, can also inhibit L-type voltage-gated calcium channels (L-VGCCs), which could contribute to reduced neuronal excitability. (aspetjournals.org)
  • Increases in the intracellular concentration of calcium ([Ca 2+ ] i ) activate various signaling pathways that lead to the expression of genes that are essential for dendritic development, neuronal survival, and synaptic plasticity. (sciencemag.org)
  • Voltage-gated Ca 2+ channels have a central role in neuronal function and are essential for converting electrical activity into biochemical events ( 1 ). (sciencemag.org)
  • Activation of the L-type Ca 2+ channel (LTC) specifically increases the expression of a group of Ca 2+ -regulated genes, including those encoding c-Fos, brain-derived neurotrophic factor (BDNF), and Bcl-2, that are important for neuronal survival, learning, and other adaptive responses in the nervous system ( 3 ). (sciencemag.org)
  • We have investigated the effects of blocking neuronal calcium channels using an organotypic hippocampal-slice model of ischemia. (ahajournals.org)
  • This damage was prevented by preincubation with omega conotoxin MVIIA, a selective N-type calcium channel blocker, and omega conotoxin MVIIC, which blocks N-type and other presynaptic neuronal calcium channels. (ahajournals.org)
  • Voltage-gated Ca 2+ channels and interacting proteins are essential in neuronal signaling and synaptic transmission during this period. (biologists.org)
  • T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing. (nih.gov)
  • Prolonged neuroinflammation produces elevation of pro-inflammatory cytokines and reactive oxygen species which can alter neuronal Ca +2 homeostasis via L-type voltage-dependent Ca +2 channels (L-VDCCs) and ryanodine receptors (RyRs). (biomedcentral.com)
  • Moreover, (3β,5α,17β)-17-hydroxyestrane-3-carbonitrile (ECN), a novel neuroactive steroid and selective T-channel antagonist, provided dose-dependent alleviation of neuropathic thermal and mechanical hypersensitivity in diabetic ob/ob mice. (diabetesjournals.org)
  • Estradiol receptor antagonist reduces ventricular arrhythmia via L-type calcium channels in chronic heart failure. (medworm.com)
  • Structure and properties of omega-agatoxin IVB, a new antagonist of P-type calcium channels. (aspetjournals.org)
  • A new peptide antagonist of voltage-activated calcium channels was purified from venom of the funnel web spider, Agelenopsis aperta. (aspetjournals.org)
  • is certainly a selective serotonin antagonist that works on the 5-HT type 3 (5-HT3) receptor. (healthcarecoremeasures.com)
  • Abstract -The amplitude of the whole-cell L-type Ca 2+ channel current recorded from vascular smooth muscle cells is reportedly greater in spontaneously hypertensive rats (SHR) than in Wistar-Kyoto rats (WKY). (ahajournals.org)
  • We examined the lateral membrane mobility of presynaptic L-type Ca 2+ channels at photoreceptor ribbon synapses of the tiger salamander ( Ambystoma tigrinum ) retina. (jneurosci.org)
  • Our results show that Ca V channels at rod and cone synapses are not fixed, but move within a membrane domain equal to or slightly larger than the area beneath the synaptic ridge at the base of the ribbon. (jneurosci.org)
  • Pharmacological disruption of the cytoskeleton or membrane cholesterol significantly increased the dimensions of the confinement domain of Ca V channels, suggesting that macromolecular scaffolds are important for organizing the synapse. (jneurosci.org)
  • SK channels are unique in that they are gated solely by intracellular Ca 2+ and hence, function to integrate intracellular Ca 2+ and membrane potentials on a beat-to-beat basis in the heart. (ahajournals.org)
  • T-type calcium channels are low voltage activated calcium channels that become deinactivated during cell membrane hyperpolarization but then open to depolarization. (wikipedia.org)
  • Like any other channel in a cell membrane, the primary function of the T-type voltage gated calcium channel is to allow passage of ions, in this case calcium, through the membrane when the channel is activated. (wikipedia.org)
  • When membrane depolarization occurs in a cell membrane where these channels are embedded, they open and allow calcium to enter the cell, which leads to several different cellular events depending on where in the body the cell is found. (wikipedia.org)
  • On the other hand, the number of radiolabeled dihydropyridine (PN200-110) bindings to the aorta of SHR did not differ from that of WKY, 4 5 suggesting that the density of Ca 2+ channels in the membrane is not increased in SHR. (ahajournals.org)
  • In the present study, we show that site-specific N-glycosylation of Ca v 3.2 is essential to stabilize expression of the channel at the plasma membrane. (springer.com)
  • In contrast, elevated external glucose concentration appears to potentiate intracellular forward trafficking of the channel to the cell surface, resulting in an increased steady-state expression of the channel protein at the plasma membrane. (springer.com)
  • The rapid rise in LV pressure likely results in myocardial cell membrane stretch and deformation of the cell membrane with resultant activation of mechanosensitive ion channels. (thefreelibrary.com)
  • The L-type calcium channel ([I.sub.Ca,L]) may also be activated by cell membrane stretch with resultant calcium influx into the cell (Figure 1) [8, 9]. (thefreelibrary.com)
  • We sought to understand these processes by studying L-Type Calcium Channel (LTCC) activity and sub-type-specific βAR-cAMP signaling within cardiomyocyte membrane microdomains. (frontiersin.org)
  • An early cellular response of osteoblasts to swelling is plasma membrane depolarization, accompanied by a transient increase in intracellular calcium ([Ca 2+ ] i ), which initiates regulatory volume decrease (RVD). (springer.com)
  • The authors have previously demonstrated a hypotonically induced depolarization of the osteoblast plasma membrane, sufficient to open L-type Ca channels and mediate Ca 2+ influx. (springer.com)
  • Electrophysiological measurements revealed elevated membrane capacitance in RV myocytes indicative of RV hypertrophy, and T-type current density was also increased. (ahajournals.org)
  • Cell membrane depolarization, followed by activation of Ca v , and calcium influx, has been suggested to inhibit renin release. (ahajournals.org)
  • The ion channels responsible for setting the membrane potential of JG cells are not known with certainty. (ahajournals.org)
  • Synaptic transmission induces depolarization in the postsynaptic membrane and activates the L-type voltage sensitive Ca 2+ channels (L-VSCC). (asahq.org)
  • Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. (biomol.com)
  • Ca V 2.2 (N-type) and Ca V 1.2 (L-type) calcium channels gate differently in response to membrane depolarization, which is critical to the unique physiological functions mediated by these channels. (elsevier.com)
  • Ion channels are integral membrane proteins that help establish and control the small voltage gradient across the plasma membrane of living cells by allowing the flow of ions down their electrochemical gradient. (creativebiomart.net)
  • L-type (CaV1.2) voltage-gated calcium channels play critical roles in membrane excitability, gene expression, cardiac and smooth muscle contraction. (nus.edu.sg)
  • The pore is formed by the alpha-1 subunit which incorporates the conduction pore, the voltage sensor and gating apparatus, and the known sites of channel regulation by second messengers, drugs, and toxins [ PMID: 14657414 ]. (ebi.ac.uk)
  • Structure and regulation of voltage-gated Ca2+ channels. (ebi.ac.uk)
  • To investigate the up regulation of cardiac T-type Ca 2+ channels in vivo , rats were maintained in chronic hypoxia, where they developed significantly elevated RV systolic pressure, RV hypertrophy and reduced cardiac output. (ahajournals.org)
  • These findings support a novel role for CRMP-2 in the regulation of N-type Ca 2+ channels and in transmitter release. (biologists.org)
  • Regulation of presynaptic Ca 2+ channels and interacting proteins has a significant impact on synaptic strength. (biologists.org)
  • Improper function and regulation of these Ca 2+ channels contributes to epilepsy, migraine, ataxia and other neurological diseases. (biologists.org)
  • Calcium regulation: Isn't that spatial? (deepdyve.com)
  • In conclusion this thesis not only supports the notion of L-type Ca2+ channels being essential for beta-cell function but also reveals new aspects that help to understand their regulation in health and disease with the prospect of this being of relevance for future scientific work. (avhandlingar.se)
  • Souvannakitti D, Nanduri J, Yuan G, Kumar GK, Fox AP, Prabhakar NR. NADPH oxidase-dependent regulation of T-type Ca2+ channels and ryanodine receptors mediate the augmented exocytosis of catecholamines from intermittent hypoxia-treated neonatal rat chromaffin cells. (uchicago.edu)
  • Protein kinase A activity controls the regulation of T-type CaV3.2 channels by Gbetagamma dimers. (uchicago.edu)
  • In this study, we investigated the regulation of CRAC channel function by extracellular Ca(2+) for channels composed primarily of Orai1, Orai2, and Orai3, by co-expressing these proteins together with Stim1, as well as the endogenous channels in HEK293 cells. (unboundmedicine.com)
  • Intracellular calcium overload underlies the mechanism of VF in catecholaminergic polymorphic ventricular tachycardia (CPVT). (thefreelibrary.com)
  • Intracellular calcium overload may also contribute to arrhythmogenesis in the Long QT Syndrome (LQTS), particularly in the Timothy syndrome [10]. (thefreelibrary.com)
  • In the current experiment we test the hypothesis that chest wall impact activates [I.sub.Ca,L], causing an intracellular calcium spike, which can result in early-after-depolarizations (EADs) or delayed-after-depolarizations (DADs) and induce VF. (thefreelibrary.com)
  • Verapamil, a synthetic papaverine derivative, primarily blocks ICa L but also may have some blocking effect on the ryanodine receptor, both of which may contribute to intracellular calcium overload. (thefreelibrary.com)
  • Alterations in intracellular calcium (Ca 2+ ) have a significant impact on Ca 2+ signaling, an integral part of the cardiac response to pathological conditions. (ahajournals.org)
  • Vasodilators generally stimulate renin release by increasing the intracellular concentration of cAMP and vasoconstrictors generally inhibit renin release by increasing the intracellular calcium concentration. (ahajournals.org)
  • At most synapses, presynaptic Ca 2+ channels are positioned near vesicle release sites, and increasing this distance reduces synaptic strength. (jneurosci.org)
  • but the mobility of presynaptic Ca V channels has not been explored. (jneurosci.org)
  • Consistent with the proposal that synaptic vesicle fusion may cause a disorganization of presynaptic release proteins ( Neher and Sakaba, 2008 ), we found that fusion of adjacent synaptic vesicles caused brief jumps in Ca V channel position, propelling channels toward the edge of the confinement domain. (jneurosci.org)
  • Neurotransmitter release is triggered by Ca 2+ entry through presynaptic voltage-dependent Ca 2+ channels ( Katz, 1969 ). (jneurosci.org)
  • 5. The properties of the presynaptic BK channel are well suited for rapid activation during the presynaptic depolarization and Ca2+ influx that are associated with transmitter release. (nih.gov)
  • this interaction induces a deacrease in the number of presynaptic functional CACNA1B channels at the cell surface (PubMed:24709664). (rcsb.org)
  • We recently identified the presynaptic N-type voltage-gated Ca 2+ channel (Cav2.2) as a CRMP-2-interacting partner. (biologists.org)
  • A variety of interactions between Ca 2+ channels and presynaptic proteins contribute to the molecular and mechanistic complexities of the vesicle release cycle and synaptic transmission ( Sudhof, 1995 ). (biologists.org)
  • There is evidence that migraine, Alzheimer's disease, and epilepsy involve a gain-of-function of the channel, leading to abnormal presynaptic vesicle release. (eurekaselect.com)
  • Cav2.1[EFb] channels show somatic, proximal and distal dendritic localization while Cav2.1[EFa] channels are expressed in the cell bodies, proximal dendrites as well as presynaptic terminals. (nus.edu.sg)
  • N-type ('N' for "Neural-Type" ) calcium channels are found primarily at presynaptic terminals and are involved in neurotransmission . (ipfs.io)
  • Multiple types of high-voltage-activated Ca 2+ channels trigger neurotransmitter release at the mammalian central synapse. (jneurosci.org)
  • N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin-IIIA (omega-Aga-IIIA). (rcsb.org)
  • We studied the sensitivity of GABAergic paired pulse depression (PPD) as a common form of STP to selective N-type high-voltage-activated Ca 2+ channels blocker omega-conotoxin (ω-CgTx). (begellhouse.com)
  • Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. (drugbank.com)
  • In the second study we found that glucose stimulation of an insulin secreting cell line induces the internalization of the L-type channel isoform Cav1.2. (avhandlingar.se)
  • In the last part of this thesis we gathered genetic, molecular and functional data about the two main L-type Ca2+ channel isoforms Cav1.2 and Cav1.3 in order to identify significant differences that may allow for development of currently unavailable isoform specific drugs. (avhandlingar.se)
  • Specifically, Cav1.2 is a cardiac L-type calcium channel and is important for excitation and contraction of the heart. (creativebiomart.net)
  • This study provides essential evidence for the molecular diversity of CaV1.2 calcium channels in the cardiovascular system. (nus.edu.sg)
  • Calmodulin supports both inactivation and facilitation of L-type calcium channels. (nih.gov)
  • Among the many types of voltage-gated Ca2+ channel, L-type Ca2+ channels particularly display inactivation and facilitation, both of which are closely linked to the earlier entry of Ca2+ ions. (nih.gov)
  • Another important facet of the T-type voltage gated calcium channel is its fast voltage-dependent inactivation compared to that of other calcium channels. (wikipedia.org)
  • Because the T-type channels are voltage dependent, hyperpolarization of the cell past its inactivation voltage will close the channels throughout the SA node, and allow for another depolarizing event to occur. (wikipedia.org)
  • All GABA A R modulators induced a negative shift in the steady-state inactivation curve of Ca v 1.3 channels, but only BDZs and pentobarbital induced a negative shift in Ca v 1.2 channel inactivation. (aspetjournals.org)
  • The corresponding mutations affect the T-type calcium channel CCA-1 and symmetrically re-tune its voltage-dependencies of activation and inactivation towards more hyperpolarized potentials. (elifesciences.org)
  • Although N-channel P o during individual sweeps at +40 mV was often high (∼0.8), mean P o was reduced by null sweeps, low P o gating, inactivation, and slow activation. (rupress.org)
  • Effects on permeation were isolated using instantaneous current-voltage relationships (IIV) after strong, brief depolarizations to activate channels with minimal inactivation. (deepdyve.com)
  • The n5209 mutation changes the voltage-dependence of steady-state activation and inactivation of T-type channels. (elifesciences.org)
  • A particularity of this type of channel is an opening at quite negative potentials and a voltage-dependent inactivation. (nih.gov)
  • An inner pore residue (Asn406) in the Nav1.5 channel controls slow inactivation and enhances mibefradil block to T-type Ca2+ channel levels. (uchicago.edu)
  • Angiotensin converting enzyme (ACE) inhibitors are another type of medication for high blood pressure and a variety of heart conditions. (medicalnewstoday.com)
  • The naturally occurring ù-conotoxins have activity at various Ca channels including the N- (Cav2.2), P/Q- (Cav2.1), R- (Cav2.3), and T- (Cav3.1/3.2) type channels and have served as platforms for the development of therapeutic agents now in development. (pharmiweb.com)
  • Here, we examine the localization and functional expression of the T-type calcium channel subunit, CaV3.1, in bipolar cells of the macaque monkey retina. (arvojournals.org)
  • Evaluation of a Two-Site, Three-Barrier Model for Permeation in CaV3.1 (α1G) T-Type Calcium. (deepdyve.com)
  • Additionally, the report provides an overview of key players involved in Voltage Dependent T Type Calcium Channel Subunit Alpha 1G (Voltage Gated Calcium Channel Subunit Alpha Cav3.1 or CACNA1G) targeted therapeutics development and features dormant and discontinued projects. (globalmarketsdirect.com)
  • The report analyses the pipeline products across relevant therapy areas under development targeting Voltage Dependent T Type Calcium Channel Subunit Alpha 1G (Voltage Gated Calcium Channel Subunit Alpha Cav3.1 or CACNA1G). (globalmarketsdirect.com)
  • The report provides a snapshot of the Global therapeutic landscape for Voltage Dependent T Type Calcium Channel Subunit Alpha 1G (Voltage Gated Calcium Channel Subunit Alpha Cav3.1 or CACNA1G). (globalmarketsdirect.com)
  • The report reviews Voltage Dependent T Type Calcium Channel Subunit Alpha 1G (Voltage Gated Calcium Channel Subunit Alpha Cav3.1 or CACNA1G) targeted therapeutics under development by companies and universities/research institutes based on information derived from company and industry-specific sources. (globalmarketsdirect.com)
  • The report reviews key players involved in Voltage Dependent T Type Calcium Channel Subunit Alpha 1G (Voltage Gated Calcium Channel Subunit Alpha Cav3.1 or CACNA1G) targeted therapeutics and enlists all their major and minor projects. (globalmarketsdirect.com)
  • The report assesses Voltage Dependent T Type Calcium Channel Subunit Alpha 1G (Voltage Gated Calcium Channel Subunit Alpha Cav3.1 or CACNA1G) targeted therapeutics based on Mechanism of Action (MoA), Route of Administration (RoA) and Molecule Type. (globalmarketsdirect.com)
  • The report reviews latest news and deals related to Voltage Dependent T Type Calcium Channel Subunit Alpha 1G (Voltage Gated Calcium Channel Subunit Alpha Cav3.1 or CACNA1G) targeted therapeutics. (globalmarketsdirect.com)
  • Identify and understand the targeted therapy areas and indications for Voltage Dependent T Type Calcium Channel Subunit Alpha 1G (Voltage Gated Calcium Channel Subunit Alpha Cav3.1 or CACNA1G). (globalmarketsdirect.com)
  • We further showed that, during windup, NMDA receptors provide a critical excitatory component in a dynamic balance of excitatory and inhibitory inputs which ultimately activates L -type calcium channels. (wiley.com)
  • 5 MAP kinase has been shown to be activated by calcium influx through both N -methyl-D-aspartate (NMDA) receptors and L-type Ca 2+ channels. (asahq.org)
  • Where they terminate at a synapse, nociceptors have a unique set of ion channels and receptors which control release of pain neurotransmitters. (painonline.com)
  • A similar transient contribution of N-type channels to neuromuscular transmission was found in neonatal rats ( Rosato Siri and Uchitel, 1999 ). (jneurosci.org)
  • Different experimental studies within the 1970s allowed for the distinction of T-type calcium channels (transient opening calcium channels) from the already well-known L-type calcium channels (Long-Lasting calcium channels). (wikipedia.org)
  • We propose that these channels serve to boost signaling within transient visual pathways. (arvojournals.org)
  • Recently, transient receptor potential channel, canonical type 3 ( TRPC 3), has been shown to localize to the mitochondria and to play a role in maintaining mitochondrial calcium homeostasis. (ahajournals.org)
  • A heterogenous group of transient or low voltage activated type CALCIUM CHANNELS. (uchicago.edu)
  • Here, we show how GSCs can be targeted by the FDA-approved drug mibefradil, which inhibits the T-type calcium channel Cav3.2. (aacrjournals.org)
  • Application of mibefradil, a T-type calcium channel blocker, to sural nerve receptive fields increased mechanical thresholds of Aβ-, Aδ- and C-fibers, confirming the functional involvement of accumulated channels in the sural nerve in SNI rats. (frontiersin.org)
  • NFAT activation was markedly stimulated by over expressing the human Ca v 3.2 T-type Ca 2+ channel cDNA in NRVM, and this activation was inhibited by cyclosporin A (a calcineurin inhibitor), by T-type selective concentrations of mibefradil and NiCl 2 , and in the absence of extracellular Ca 2+ . (ahajournals.org)
  • A novel mibefradil derivative, NNC55-0396, designed to be hydrolysis-resistant, was shown to be a selective T-type Ca 2+ channel inhibitor without L-type Ca 2+ channel efficacy. (aspetjournals.org)
  • T-type calcium channels belong to the 'low-voltage activated (LVA)' group and are strongly blocked by mibefradil. (nih.gov)
  • Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. (rcsb.org)
  • Calcium ions play a vital role in cellular and organism physiology. (nc3rs.org.uk)
  • A gene on chromosome 1q25-q31 that encodes the alpha-1E subunit of a voltage-dependent calcium channel, which mediates the entry of calcium ions into excitable cells. (thefreedictionary.com)
  • Whereas some ion channels permit the passage of ions based on charge, others conduct based on a ionic species, such as sodium or potassium. (creativebiomart.net)
  • Collectively, our data further support a role for Ca v 3.2 channels in peripheral nociception and identify a novel mechanism for Ca v 3.2 modulation that underlies nociceptor sensitization. (jneurosci.org)
  • The report provides detailed coverage of the pipeline landscape for this mechanism of action, equipped with data from multiple sources with complete pipeline analysis by developmental stage, associated indications, route of administration and molecule type. (reportbuyer.com)
  • This approach has allowed us to separate the Ca 2+ -conducting properties of the LTC from its signaling properties and has provided insight into the mechanism by which voltage-gated channels regulate gene expression. (sciencemag.org)
  • Our results indicate that T-type calcium channels are critical regulators of a C. elegans serotonergic circuit and demonstrate a mechanism in which T-type channels functionally gate inhibitory modulation in vivo . (elifesciences.org)
  • Introduction: Functional and structural diversity among voltage-gated calcium channels is an important mechanism employed by cells to optimize calcium dependent signaling. (sid.ir)
  • The report provides comprehensive information complete with Analysis by Indications, Stage of Development, Mechanism of Action (MoA), Route of Administration (RoA) and Molecule Type. (globalmarketsdirect.com)
  • Moreover, the possible role of auxiliary subunit composition of the channels in Angiotensin II modulation of L-type calcium channels has not yet been explored. (nih.gov)
  • Ca(v)β(2a) containing channels were insensitive to modulation and this effect was partially due to the N-terminal palmitoylation sites of this subunit. (nih.gov)
  • This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 concerning Zalicus, its product candidate Z944, its potential and the plans for its further clinical preclinical development, the Zalicus selective Ion channel modulation technology and its other business plans. (aol.com)
  • Although the effective treatment of chronic pain remains elusive, recent findings suggest the importance of T-channels in peripheral nociception, raising the possibility that modulation of those channels might be therapeutic in the treatment of acute ( 6 , 7 ) and chronic ( 8 ) pain. (diabetesjournals.org)
  • The modulation of calcium channels by the actin cytoskeleton or actin-binding proteins (ABP) is not well understood. (hindawi.com)
  • L-channels lack this response to roscovitine, which allowed us to use N-L chimeras to test the role of domain III in roscovitine modulation of N-channel deactivation. (elsevier.com)
  • Robust Ca 2+ channel modulation required coexpression of both Gβ and Gγ. (elsevier.com)
  • Furthermore, changes in SK channel activation kinetics following SR Ca 2+ depletion suggest both LTCC-mediated Ca 2+ influx and SR Ca 2+ release are necessary for the activation of cardiac SK channels. (ahajournals.org)
  • Here, we examine the gating kinetics of single N-channels. (rupress.org)
  • As a first step, we examined the effect of domain exchange between N-type and L-type channels on activationdeactivation kinetics, which were significantly different between these channels. (elsevier.com)
  • Here we focus on new research describing a constituent of the venom from the Brazilian Wandering Spider as another Cav2.2 channel blocker. (pharmiweb.com)
  • Cav2.2 (N-type) channels were most sensitive to PnTx3-6, blocked at low nanomolar potency, with activity observed in both transfected HEK cells and neuroblastoma cell lines. (pharmiweb.com)
  • Further research is continuously occurring to better understand these distinct channels, as well as to create drugs to selectively target these channels. (wikipedia.org)
  • Under the terms of the agreement, Neuromed grants Merck an exclusive worldwide license to research, develop and commercialize NMED-160 and other compounds that selectively target the N-type calcium channel. (bionity.com)
  • The features of the LTC that specify its functions are not known, but one possibility is that Ca 2+ -binding proteins bound to the channel sense the local Ca 2+ concentration and selectively activate signaling pathways when the channel opens. (sciencemag.org)
  • L-type calcium channels selectively signal to the nucleus. (sciencemag.org)
  • An atrial myocyte cell line (HL-1) that selectively expresses T-type calcium current was employed to show that inhibiting calcium influx through the T-type calcium channel inhibits cellular proliferation. (illinois.edu)
  • N-type calcium channels are important for neurotransmitter release at synapses of the peripheral and central nervous system. (rupress.org)
  • These channels are also involved in various calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and apoptosis. (thefreedictionary.com)
  • The distinct subcellular localization of Cav2.1[EFa] and Cav2.1[EFb] channels suggests compartmentalized roles of voltage-gated Ca2+ channels in neurotransmitter release and generation of synaptic plasticity. (nus.edu.sg)
  • [6] Strong depolarization by an action potential causes these channels to open and allow influx of Ca 2+ , initiating vesicle fusion and release of stored neurotransmitter. (ipfs.io)
  • CONCLUSIONS Our results indicate that pharmacological antagonism of T-channels is potentially an important novel therapeutic approach for the management of painful diabetic neuropathy. (diabetesjournals.org)
  • Pharmacological evidence of T-type calcium channels suggest that they play a role in several forms of cancer, absence epilepsy, pain, and Parkinson's disease. (wikipedia.org)
  • Thus a combination of kinetic and pharmacological evidence supports the hypothesis that domain III is an important regulator of N-channel closing. (elsevier.com)
  • Among them, the ω-conotoxin GVIA-sensitive N-type channels and the ω-Aga-IVA-sensitive P/Q-type channels mediate fast synaptic transmission. (jneurosci.org)
  • Our results indicate that N-type channels contribute to thalamic and cerebellar IPSCs only transiently during early postnatal period and P/Q-type channels predominantly mediate mature synaptic transmission, as we reported previously at the brainstem auditory synapse formed by the calyx of Held. (jneurosci.org)
  • Makarenko VV, Ahmmed GU, Peng YJ, Khan SA, Nanduri J, Kumar GK, Fox AP, Prabhakar NR. CaV3.2 T-type Ca2+ channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia. (uchicago.edu)
  • Zalicus applies its expertise in the discovery and development of selective ion channel modulators and its combination high throughput screening capabilities to discover innovative therapeutics for itself and its collaborators in the areas of pain, inflammation, oncology and infectious disease. (aol.com)
  • By means of extracellular recordings in the dorsal horn, we showed that windup of dorsal horn neuron discharge was sensitive to the modulators of L -type calcium current. (wiley.com)
  • In skeletal muscle, the L-type calcium channels act as a voltage sensor for excitation-contraction coupling, and in cardiac muscle, they provide a pathway for calcium influx. (ebi.ac.uk)
  • Aβ-, Aδ- and C-fibers of the uninjured sural nerve were sensitized revealed by in vivo single-unit recording, which were accompanied by accumulation of Ca v 3.2 T-type calcium channel proteins shown by Western blotting. (frontiersin.org)
  • In addition, a yeast-two-hybrid screen was performed to find potential interacting proteins with the EF-hand of the Cav2.1[EFa] channel. (nus.edu.sg)
  • The recent discoveries of Stim1 and Orai proteins have shed light on the molecular makeup of both the endoplasmic reticulum Ca(2+) sensor and the calcium release-activated calcium (CRAC) channel, respectively. (unboundmedicine.com)
  • Certain proteins such as caveolins and Ca2+ channels found in the heart control the cardiac contractile function and could offer protection during hypertrophy. (grantome.com)
  • The authors further demonstrate that substrate interaction determines which specific α 1 Ca channel subunit isoform predominates and mediates Ca 2+ entry and RVD. (springer.com)
  • This α1 subunit is also known as the calcium channel, voltage-dependent, R type, alpha 1E subunit (CACNA1E) or Cav2.3 which in humans is encoded by the CACNA1E gene. (wikipedia.org)
  • The Ca v 2.2 gene whic h encodes the functional core of the N-type calcium channels ( a 1B ( has the potential to generate several Ca v 2.2 splice variants with different properties. (sid.ir)
  • This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. (biomol.com)
  • Mutations in this gene have been shown to cause incomplete X-linked congential stationary night blindness type 2 (CSNB2). (creativebiomart.net)
  • This gene encodes a T-type, low-voltage activated calcium channel. (nih.gov)
  • The α 1 subunit is also known as the calcium channel, voltage-dependent, N type, alpha 1B subunit ( CACNA1B ) or Ca v 2.2 [1] which in humans is encoded by the CACNA1B gene . (ipfs.io)
  • Like the others of this class, the α1 subunit forms the pore through which calcium enters the cell and determines most of the channel's properties. (wikipedia.org)
  • The α1 subunit of T-type channels is the primary subunit that forms the pore of the channel, and allows for entry of calcium. (wikipedia.org)
  • As with other sub-types of voltage-gated calcium channel, the α 1 subunit forms the pore through which calcium enters the cell and determines most of the channel's properties. (ipfs.io)
  • The functional properties of bipolar cells are shaped by the inventory and sub-cellular distribution of voltage-gated ion channels they express. (arvojournals.org)
  • These voltage-gated ion channels can contribute to several functional reqirements of ganglion cells. (arvojournals.org)
  • This study aimed at identifying the type and functional significance of potassium channels and voltage-dependent calcium channels (Ca v ) in single rat JG cells using whole-cell patch clamp. (ahajournals.org)
  • We conclude that JG cells express functional cAMP-sensitive BK Ca channels (the ZERO splice variant) and voltage-dependent L-type Ca 2+ channels. (ahajournals.org)
  • To examine the role of calcium channels in depolarization-activated cholecystokinin (CCK) release, studies were performed in an intestinal CCK-secreting cell line, STC-1. (rti.org)
  • This is very important for the heart when stimulated by the sympathetic nervous system that causes the heart rate to increase, in that not only does the T-type calcium channel provide an extra depolarization punch in addition to the voltage gated sodium channels to cause a stronger depolarization, but it also helps provide a quicker depolarization of the cardiac cells. (wikipedia.org)
  • Therefore, while they help provide stronger and quicker depolarization of cardiac muscle cells and thalamus nerve cells, T-type channels also allow for more frequent depolarization events. (wikipedia.org)
  • With 100 mM Ba 2+ in the pipet, mean N-channel open probability ( P o , measured over 100 ms) increased with depolarization, but the range at a single voltage was large (e.g. (rupress.org)
  • We selected most pathways CACNA1C participated on our site, such as MAPK signaling pathway, Calcium signaling pathway, Cardiac muscle contraction, which may be useful for your reference. (creativebiomart.net)
  • The present study aims to investigate the possible contribution of Ca v 3.2 T-type calcium channels in uninjured afferent nerve fibers to neuropathic pain in rats with spared nerve injury (SNI). (frontiersin.org)
  • These results suggest that axonal accumulation of Ca v 3.2 T-type calcium channels plays an important role in the uninjured sural nerve sensitization and contributes to neuropathic pain. (frontiersin.org)
  • The pore-forming α1 subunit of T-type channels has at least three subtypes, α1G (Ca v 3.1), α1H (Ca v 3.2) and α1I (Ca v 3.3). (frontiersin.org)
  • These channels are examples of molecular signal-transduction units that regulate themselves through their own activity. (nih.gov)
  • Despite extensive biophysical analysis, the molecular basis of autoregulation remains unclear, although a putative Ca2+-binding EF-hand motif and a nearby consensus calmodulin-binding isoleucine-glutamine ('IQ') motif in the carboxy terminus of the alpha1C channel subunit have been implicated. (nih.gov)
  • Thus, although Ca V channels are mobile, molecular scaffolds confine them beneath the ribbon to maintain neurotransmission even at high release rates. (jneurosci.org)
  • We conclude that Ca V channels are mobile, but molecular scaffolds maintain channels within a confinement area beneath the ribbon to support synaptic release even at high rates. (jneurosci.org)
  • However, the molecular mechanisms underlying the functions of T-channels in nociceptors are poorly understood. (jneurosci.org)
  • Another area that is being extensively mined for new molecular targets includes the voltage-activated Ca channels. (pharmiweb.com)
  • This represents the first molecular identification of the Ca channels that transduce the initiation signal for RVD by osteoblastic cells. (springer.com)
  • We have used the patch-clamp technique in combination with molecular techniques to define the ion channels involved in the outward current and to study the presence of Ca v in JG cells and their possible interaction with the secretory process. (ahajournals.org)
  • They are poorly understood, but like Q-type calcium channels , they appear to be present in cerebellar granule cells. (bionity.com)
  • In contrast to thalamic and cerebellar IPSCs and brainstem auditory EPSCs, N-type Ca 2+ channels persistently contribute to cerebral cortical EPSCs and spinal IPSCs throughout postnatal months. (jneurosci.org)
  • On the basis of their voltage activation properties, the voltage-gated calcium classes can be further divided into two broad groups: the low (T-type) and high (L, N, P, Q and R-type) threshold-activated channels. (ebi.ac.uk)
  • Within cardiac muscle cell and smooth muscle cells voltage-gated calcium channel activation initiates contraction directly by allowing the cytosolic concentration to increase. (wikipedia.org)
  • Although all of these functions of the T-type voltage gated calcium channel are important, quite possibly the most important of its functions is its ability to generate potentials that allow for rhythmic bursts of action potentials in cardiac cells of the sinoatrial node of the heart and in the thalamus of the brain. (wikipedia.org)
  • Electrophysiological experiments, carried out on mouse pancreatic B-cells, showed that glacontryphan-M blocks L-type voltage-gated calcium ion channel activity in a calcium-dependent manner. (lu.se)
  • CACNA1C has several biochemical functions, for example, calcium channel activity, high voltage-gated calcium channel activity, ion channel activity. (creativebiomart.net)
  • We present a series of three patients with a myasthenic syndrome, dropped-head syndrome, bulbar and respiratory muscle weakness and positive testing for anti-N-type voltage-gated calcium channel antibodies. (pagepressjournals.org)
  • In two cases anti-acetylcholin receptor antibodies were elevated, anti-P/Q-type voltage-gated calcium channel antibodies were negative. (pagepressjournals.org)
  • Our patients showed features of pre- and postsynaptic myasthenic syndrome as well as severe dropped-head syndrome and bulbar and axial muscle weakness, but only anti-N-type voltage-gated calcium channel antibodies were positive. (pagepressjournals.org)
  • The variability in mean P o across patches resulted from differences in the frequency these different gating processes were expressed by the channels. (rupress.org)
  • While P o of the main N-channel gating state is high, the net P o is reduced to a maximum value of close to 0.5 by other gating processes. (rupress.org)
  • Our studies of the e37a/e37b splice site reveal a multifunctional domain in the C-terminus of Ca(V)2.2 that regulates the overall activity of N-type calcium channels in nociceptors. (painonline.com)
  • The channel activity is directed by the pore-forming and voltage-sensitive alpha-1 subunit. (rcsb.org)
  • Swelling-induced [Ca 2+ ] i transients, and RVD in cells grown on a type I collagen matrix, are inhibited by removal of Ca from extracellular solutions, dihydropyridines, and antisense oligodeoxynucleotides directed exclusively to the α 1C isoform of the L-type Ca channel. (springer.com)
  • Ca 2+ transients and RVD in cells grown on untreated glass cover slips were inhibited by similar maneuvers, but only by antisense oligodeoxynucleotides directed to the α 1S isoform of the L-type Ca channel. (springer.com)
  • However, which L-type isoform is operative in human beta-cells and how the L-type channels may be regulated in health and disease are two questions that remain unanswered and formed the basis for this thesis. (avhandlingar.se)
  • The third study revealed that the L-type Ca2+ channel isoform Cav1.3 is the major isoform in enriched human beta-cells and that islets of type 2 diabetes patients express reduced levels of Cav1.3 mRNA than controls. (avhandlingar.se)
  • Evidence for two distinct types of potassium-activated calcium channels in an intestinal smooth muscle. (aspetjournals.org)
  • The corresponding influx of calcium serves to trigger secretion of CCK. (rti.org)
  • Influx of calcium into the cell through the L-type channel is responsible for excitation-contraction coupling in the heart. (illinois.edu)
  • The results show that Ca 2+ channels are dynamic and move within a confined region beneath the synaptic ribbon. (jneurosci.org)
  • Fusion of nearby synaptic vesicles caused jumps in Ca 2+ channel position, propelling them toward the outer edge of the confinement domain. (jneurosci.org)
  • However, at most central synapses, it is not known whether the contributions of different Ca 2+ channel types to synaptic transmission remain stable throughout postnatal development. (jneurosci.org)
  • Thus, in adult animals, synaptic transmission is predominantly mediated by P/Q-type channels at a subset of synapses and mediated synergistically by multiple types of Ca 2+ channels at other synapses. (jneurosci.org)
  • Recently, however, the contribution of N-type Ca 2+ channels to rat auditory brainstem synaptic transmission was found to be restricted to the early postnatal period ( Iwasaki and Takahashi, 1998 ). (jneurosci.org)
  • These findings raise the possibility that the contribution of N-type Ca 2+ channels to synaptic transmission might be developmentally regulated at other CNS synapses. (jneurosci.org)
  • Although it is clear that N-type Ca 2+ channels contribute to synaptic transmission at many developing synapses, our results suggest that, at a subset of CNS synapses, there is a developmental switch to P/Q-type Ca 2+ channels. (jneurosci.org)
  • Dysregulation of Ca(v)1.4 channels disrupts the maturation of photoreceptor synaptic ribbons in congenital stationary night blindness type 2. (creativebiomart.net)
  • N-type Ca(V)2.2 calcium channels (see prior articles on these using SEARCH at this site) are found in PRE-synaptic nerve terminals. (painonline.com)
  • Among them, the L-type calcium channel is responsible for the excitation-contraction coupling of skeletal, smooth, and cardiac muscle. (nc3rs.org.uk)
  • It shares sequence characteristics with all voltage-dependent cation channels, and exploits the same 6-helix bundle structural motif - in both sodium and calcium channels, this motif is repeated 4 times within the sequence to give a 24-helix bundle. (ebi.ac.uk)