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 species of gram-positive, coccoid bacteria isolated from skin lesions, blood, inflammatory exudates, and the upper respiratory tract of humans. It is a group A hemolytic Streptococcus that can cause SCARLET FEVER and RHEUMATIC FEVER.
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.
Infections with bacteria of the genus STREPTOCOCCUS.
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.
Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.
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.

Differential distribution of three members of a gene family encoding low voltage-activated (T-type) calcium channels. (1/576)

Low voltage-activated (T-type) calcium currents are observed in many central and peripheral neurons and display distinct physiological and functional properties. Using in situ hybridization, we have localized central and peripheral nervous system expression of three transcripts (alpha1G, alpha1H, and alpha1I) of the T-type calcium channel family (CaVT). Each mRNA demonstrated a unique distribution, and expression of the three genes was largely complementary. We found high levels of expression of these transcripts in regions associated with prominent T-type currents, including inferior olivary and thalamic relay neurons (which expressed alpha1G), sensory ganglia, pituitary, and dentate gyrus granule neurons (alpha1H), and thalamic reticular neurons (alpha1I and alpha1H). Other regions of high expression included the Purkinje cell layer of the cerebellum, the bed nucleus of the stria terminalis, the claustrum (alpha1G), the olfactory tubercles (alpha1H and alpha1I), and the subthalamic nucleus (alpha1I and alpha1G). Some neurons expressed high levels of all three genes, including hippocampal pyramidal neurons and olfactory granule cells. Many brain regions showed a predominance of labeling for alpha1G, including the amygdala, cerebral cortex, rostral hypothalamus, brainstem, and spinal cord. Exceptions included the basal ganglia, which showed more prominent labeling for alpha1H and alpha1I, and the olfactory bulb, the hippocampus, and the caudal hypothalamus, which showed more even levels of all three transcripts. Our results are consistent with the hypothesis that differential gene expression underlies pharmacological and physiological heterogeneity observed in neuronal T-type calcium currents, and they provide a molecular basis for the study of T-type channels in particular neurons.  (+info)

Cloning and expression of a novel member of the low voltage-activated T-type calcium channel family. (2/576)

Low voltage-activated Ca2+ channels play important roles in pacing neuronal firing and producing network oscillations, such as those that occur during sleep and epilepsy. Here we describe the cloning and expression of the third member of the T-type family, alpha1I or CavT.3, from rat brain. Northern analysis indicated that it is predominantly expressed in brain. Expression of the cloned channel in either Xenopus oocytes or stably transfected human embryonic kidney-293 cells revealed novel gating properties. We compared these electrophysiological properties to those of the cloned T-type channels alpha1G and alpha1H and to the high voltage-activated channels formed by alpha1Ebeta3. The alpha1I channels opened after small depolarizations of the membrane similar to alpha1G and alpha1H but at more depolarized potentials. The kinetics of activation and inactivation were dramatically slower, which allows the channel to act as a Ca2+ injector. In oocytes, the kinetics were even slower, suggesting that components of the expression system modulate its gating properties. Steady-state inactivation occurred at higher potentials than any of the other T channels, endowing the channel with a substantial window current. The alpha1I channel could still be classified as T-type by virtue of its criss-crossing kinetics, its slow deactivation (tail current), and its small (11 pS) conductance in 110 mM Ba2+ solutions. Based on its brain distribution and novel gating properties, we suggest that alpha1I plays important roles in determining the electroresponsiveness of neurons, and hence, may be a novel drug target.  (+info)

L- and T-type voltage-gated Ca2+ currents in adrenal medulla endothelial cells. (3/576)

We investigated voltage-dependent Ca2+ channels of bovine adrenal medulla endothelial cells with the whole cell version of the patch-clamp technique. Depolarization elicited an inward current that was carried by Ca2+ and was composed of a transient (T) current, present in all the cells tested, and a sustained (L) current, present in 65% of them. We separated these currents and measured their individual kinetic and gating properties. The activation threshold for T current was approximately -50 mV, and its maximum amplitude was -49.8 +/- 4.8 pA (means +/- SE, n = 19) at 0 mV. The time constant was 10.2 +/- 1.5 ms (n = 4) for activation and 18.4 +/- 2.8 ms (n = 4) for inactivation. The L current activated at -40 mV, and it reached a plateau at -20.1 +/- 2.3 pA (n = 6). Its activation time course was a single exponential with an activation time contant of 26.8 +/- 2.3 ms (n = 4). Current-voltage curves, kinetics, gating, response to BAY K 8644, nifedipine, amiloride, and different selectivity for Ba2+ and Ca2+ indicated that the underlying channels for the observed currents are only of the T- and L-types that resemble those of the endocrine secretory cells.  (+info)

A role for T-type Ca2+ channels in the synergistic control of aldosterone production by ANG II and K+. (4/576)

Independently, plasma K+ and ANG II stimulate aldosterone secretion from adrenal glomerulosa (AG) cells, but together they synergistically control production. We studied mechanisms to mediate this synergy using bovine AG cells studied under physiological conditions (in 1.25 mM Ca2+ at 37 degrees C). Increasing K+ from 2 to 5 mM caused a potentiation of ANG II-induced aldosterone secretion and a substantial membrane depolarization ( approximately 21 mV). ANG II inhibited a K+-selective conductance in both 2 and 5 mM K+ but caused only a slight depolarization because, under both conditions, membrane potential was close to the reversal potential of the ANG II-induced current. ANG II activated calcium/calmodulin-dependent protein kinase II (CaMKII) equivalently in 2 and 5 mM K+. However, CaMKII activation caused a hyperpolarizing shift in the activation of T-type Ca2+ channels, such that substantially more current was elicited at membrane potentials established by 5 mM K+. We propose that synergy in aldosterone secretion results from K+-induced depolarization and ANG II-induced modulation of T-type channel activation, such that together they promote enhanced steady-state Ca2+ flux.  (+info)

Morphological transformation induced by activation of the mitogen-activated protein kinase pathway requires suppression of the T-type Ca2+ channel. (5/576)

Transformation of fibroblasts by various oncogenes, including ras, mos, and src accompanies with characteristic morphological changes from flat to round (or spindle) shapes. Such morphological change is believed to play an important role in establishing malignant characteristics of cancer cells. Activation of the mitogen-activated protein kinase (MAPK) pathway is a converging downstream event of transforming activities of many oncogene products commonly found in human cancers. Intracellular calcium is known to regulate cellular morphology. In fibroblasts, Ca2+ influx is primarily controlled by two types of Ca2+ channels (T- and L-types). Here, we report that the T-type current was specifically inhibited in cells expressing oncogenically activated Ras as well as gain-of-function mutant MEK (MAPK/extracellular signal-regulated kinase (ERK) kinase, a direct activator of MAPK), whereas treatment of ras-transformed cells with a MEK-specific inhibitor restored T-type Ca2+ channel activity. Using a T-type Ca2+ channel antagonist, we further found that suppression of the T-type Ca2+ channel by the activated MAPK pathway is a prerequisite event for the induction and/or maintenance of transformation-associated morphological changes.  (+info)

All thalamocortical neurones possess a T-type Ca2+ 'window' current that enables the expression of bistability-mediated activities. (6/576)

1. The existence of a non-negligible steady-state ('window') component of the low threshold, T-type Ca2+current (IT) and an appropriately large ratio of IT to ILeak conductance (i.e. gT/gLeak) have been shown to underlie a novel form of intrinsic bistability that is present in about 15 % of thalamocortical (TC) neurones. 2. In the present experiments, the dynamic clamp technique was used to introduce into mammalian TC neurones in vitro either an artificial, i.e. computer-generated, IT in order to enhance endogenous IT, or an artificial inward ILeak to decrease endogenous ILeak. Using this method, we were able to investigate directly whether the majority of TC neurones appear non-bistable because their intrinsic ionic membrane properties are essentially different (i.e. presence of a negligible IT 'window' component), or simply because they possess a gT or gLeak conductance that is insufficiently large or small, respectively. 3. The validity of the dynamic clamp arrangement and the accuracy of artificial IT were confirmed by (i) recreating the low threshold calcium potential (LTCP) with artificial IT following its block by Ni2+ (0.5-1 mM), and (ii) blocking endogenous LTCPs with an artificial outward IT. 4. Augmentation of endogenous IT by an artificial analog or introduction of an artificial inward ILeak transformed all non-bistable TC neurones to bistable cells that expressed the full array of bistability-mediated behaviours, i.e. input signal amplification, slow oscillatory activity and membrane potential bistability. 5. These results demonstrate the existence of a non-negligible IT 'window' component in all TC neurones and suggest that rather than being a novel group of neurones, bistable cells are merely representative of an interesting region of dynamical modes in the (gT, gLeak) parameter space that may be expressed under certain physiological or pathological conditions by all TC neurones and other types of excitable cells that possess an IT 'window' component with similar biophysical properties.  (+info)

Troglitazone inhibits voltage-dependent calcium currents in guinea pig cardiac myocytes. (7/576)

BACKGROUND: It has been suggested that intracellular Ca2+ overload in cardiac myocytes leads to the development of diabetic cardiomyopathy. Troglitazone, an insulin-sensitizing agent, is a promising therapeutic agent for diabetes and has been shown to prevent diabetes-induced myocardial changes. To elucidate the underlying mechanism of troglitazone action on cardiac myocytes, the effects of troglitazone on voltage-dependent Ca2+ currents were examined and compared with classic Ca2+ antagonists (verapamil and nifedipine). METHODS AND RESULTS: Whole-cell voltage-clamp techniques were applied in single guinea pig atrial myocytes. Under control conditions with CsCl internal solution, the voltage-dependent Ca2+ currents consisted of both T-type (ICa,T) and L-type (ICa,L) Ca2+ currents. Troglitazone effectively reduced the amplitude of ICa,L in a concentration-dependent manner. Troglitazone also suppressed ICa,T, but the effect of troglitazone on ICa,T was less potent than that on ICa,L. The current-voltage relationships for ICa,L and the reversal potential for ICa,L were not altered by troglitazone. The half-maximal inhibitory concentration of troglitazone on ICa,L measured at a holding potential of -40 mV was 6.3 micromol/L, and 30 micromol/L troglitazone almost completely inhibited ICa,L. Troglitazone 10 micromol/L did not affect the time courses for inactivation of ICa,L and inhibited ICa,L mainly in a use-independent fashion, without shifting the voltage-dependency of inactivation. This effect was different from those of verapamil and nifedipine. Troglitazone also reduced isoproterenol- or cAMP-enhanced ICa,L. CONCLUSIONS: These results demonstrate that troglitazone inhibits voltage-dependent Ca2+ currents (T-type and L-type) and then antagonizes the effects of isoproterenol in cardiac myocytes, thus possibly playing a role in preventing diabetes-induced intracellular Ca2+ overload and subsequent myocardial changes.  (+info)

The effects of verapamil and diltiazem on N-, P- and Q-type calcium channels mediating dopamine release in rat striatum. (8/576)

1. The putative inhibitory effects of verapamil and diltiazem on neuronal non-L-type Ca2+ channels were studied by investigating their effects on either K+- or veratridine-evoked [3H]-dopamine ([3H]-DA) release in rat striatal slices. Involvement of N-, P- and Q-type channels was identified by sensitivity of [3H]-DA release to omega-conotoxin GVIA (omega-CTx-GVIA), omega-agatoxin IVA (omega-Aga-IVA) and omega-conotoxin MVIIC (omega-CTx-MVIIC), respectively. 2. KCl (50 mM)-evoked [3H]-DA release was abolished in the absence of Ca2+, and was insensitive to dihydropyridines (up to 30 microM). It was significantly blocked by omega-CTx-GVIA (1 microM), omega-Aga-IVA (30 nM) and was confirmed to be abolished by omega-CTx-MVIIC (3 microM), indicating involvement of N-, P- and Q-type channel subtypes. 3. Verapamil and diltiazem inhibited K+-evoked [3H]-DA release in a concentration-dependent manner. The inhibitory effects of verapamil or diltiazem (each 30 microM) were fully additive to the effect of omega-CTx-GVIA (1 microM), whereas co-application with omega-Aga-IVA (30 nM) produced similar effects to those of omega-Aga-IVA alone. 4. As shown previously, veratridine-evoked [3H]-DA release in Ca2+ containing medium exclusively involves Q-type Ca2+ channels. Here, diltiazem (30 microM) did not inhibit veratridine-evoked [3H]-DA release, whereas verapamil (30 microM) partially inhibited it, indicating possible involvement of Q-type channels in verapamil-induced inhibition. However, verapamil (30 microM) inhibited this release even in the absence of extracellular Ca2+, suggesting that Na+ rather than Q-type Ca2+ channels are involved. 5. Taken together, our results suggest that verapamil can block P- and at higher concentrations possibly N- and Q-type Ca2+ channels linked to [3H]-DA release, whereas diltiazem appears to block P-type Ca2+ channels only.  (+info)

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. Influx of calcium into the cell through the L-type channel is responsible for excitation-contraction coupling in the heart. The T-type calcium current has been associated with growth and differentiation in a number of different cell types. 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. Drug dosage studies demonstrate that the T-type calcium channel responsible for this effect is Cav 3.1. Furthermore, blocking the calcium influx through the T-type calcium channel arrests cells in the G2/M phase of the cell cycle. Interestingly, the proliferative effect of calcium influx through the T-type calcium channel appears to happen in the early G1 phase of the cell cycle ...
Heantos-4 is a refined combination of plant extracts currently approved to treat opiate addiction in Vietnam. In addition to its beneficial effects on withdrawal and prevention of relapse, reports of sedation during clinical treatment suggest that arousal networks in the brain may be recruited during Heantos administration. T-type calcium channels are implicated in the generation of sleep rhythms and in this study we examined whether a Heantos-4 extraction modulates T-type calcium channel currents generated by the Cav3.1, Cav3.2 and Ca3.3 subtypes. Utilizing whole-cell voltage clamp on exogenously expressed T-type calcium channels we find that Heantos inhibits Cav3.1 and Cav3.3 currents, while selectively potentiating Cav3.2 currents. We further examined the effects of Heantos-4 extract on low-threshold burst-firing in thalamic neurons which contribute to sleep oscillations. Using whole-cell current clamp in acute thalamic brain slices Heantos-4 suppressed rebound burst-firing in ventrobasal
TY - JOUR. T1 - Synthesis and biological evaluation of 1-(2-hydroxy-3-phenyloxypropyl) piperazine derivatives as T-type calcium channel blockers. AU - Park, Jung Eun. AU - Ji, Wan Keun. AU - Jang, Jae Wan. AU - Pae, Ae Nim. AU - Choi, Keehyun. AU - Choi, Kihang. AU - Kang, Jahyo. AU - Roh, Eun Joo. PY - 2013/3/15. Y1 - 2013/3/15. N2 - To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 2-hydroxy-3-phenoxypropyl piperazine derivatives were synthesized and evaluated for in vitro activities. Compound 6m and 6q showed high selectivity over hERG channel (IC50 ratio of hERG/α1G 6m = 8.5, 6q = 18.38) and they were subjected to measure pharmacokinetics profiles. Among them compound 6m showed an excellent pharmacokinetic profile in rats.. AB - To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 2-hydroxy-3-phenoxypropyl piperazine derivatives were synthesized and evaluated for in vitro activities. Compound 6m and ...
4-Fluoro-Piperidine T-Type Calcium Channel Antagonists - The present invention is directed to 4-fluoro-piperidine compounds which are antagonists of T-type calcium channels, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which T-type calcium channels are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels are involved ...
Here, we report the novel findings that in human adrenal glomerulosa cells both basal and stimulated rates of aldosterone production depend on voltage-gated calcium currents through T-type as well as L-type calcium channels. These findings are surprising because patch-clamp studies consistently report the basal membrane potential of ZG cells to be very hyperpolarized (around −80 mV), a potential at which high threshold L-type calcium channels are not expected to be active. In contrast, low threshold T-type calcium channels are activated at more hyperpolarized potentials and have a permissive window of steady-state activity at more hyperpolarized potentials (Perez-Reyes 2003). When stimulated by low physiological concentrations of Ang II or small increases in extracellular potassium, the membrane potential of ZG cells can rapidly reach the permissive voltage window for persistent T-type, but not L-type, calcium channel activity, that allows steady-state calcium influx (Rossier 2016). Therefore, ...
1. A method for preventing or treating hypercardia, heart failure, cardiomyopathy, atrial fibrillation, tachyarrhythmia, arterial sclerosis, nephritis, nephropathy, renal disorder, renal insufficiency, inflammation, edema, hyper-aldosteronism, neurogenic pain, epilepsy or cancer, comprising:administering to a subject in need thereof an effective amount of a T-type calcium channel blocker having a nitrogen-containing hetero ring moiety of formula (1) ##STR00015## or a pharmaceutically acceptable salt thereof,wherein Ar1 of formula (1) is a substituent selected from the group consisting of a phenyl group, a pyridyl group, a furyl group or a 2,1,3-benzoxadiazol-4-yl group;wherein the Ar1 substituent may be optionally substituted with one or two substituents selected from the group consisting of NO2, CF3, Br, Cl, F, C1-20 alkyl group, OH, OR6, OCHF2, COOR6, NH2, NHR6, NR6R7, CONH2, CONHR6, CONR6R7, COSR6, SR6, S(O)R6, S(O)2R6, SO3H, SO3R6, SO2NH2, SO2NHR6, SO2NR6R7, CN and phenyloxy group, ...
Zalicus Advancing Clinical Development of Z944, Its Novel, Oral, T-Type Calcium Channel Blocker, for the Treatment of Pain Experimental Clinical Study Expected to Initiate Third Quarter 2013 CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Zalicus Inc.
T-type calcium channels and cannabinoid receptors are known to play important roles in chronic pain, making them attractive therapeutic targets. We recently reported on the design, synthesis and analgesic properties of a novel T-type channel inhibitor (NMP-7), which also shows mixed agonist activity on CB1 and CB2 receptors in vitro. Here, we analyzed the analgesic effect of systemically delivered NMP-7 (intraperitoneal (i.p.) or intragstric (i.g.) routes) on mechanical hypersensitivity in inflammatory pain induced by Complete Freunds Adjuvant (CFA) and neuropathic pain induced by sciatic nerve injury. NMP-7 delivered by either i.p. or i.g. routes produced dose-dependent inhibition of mechanical hyperalgesia in mouse models of inflammatory and neuropathic pain, without altering spontaneous locomotor activity in the open-field test at the highest active dose. Neither i.p. nor i.g. treatment reduced peripheral inflammation per se, as evaluated by examining paw edema and myeloperoxidase activity. The
TY - JOUR. T1 - A model of the T-type calcium current and the low-threshold spike in thalamic neurons. AU - Wang, X. J.. AU - Rinzel, J.. AU - Rogawski, Michael A. PY - 1991. Y1 - 1991. N2 - A model of the transient, low-threshold voltage-dependent (T-type) Ca2+ current is constructed using recent whole-cell voltage-clamp data from enzymatically isolated rat thalamocortical relay neurons. The T-type Ca2+ current is described according to the Hodgkin-Huxley scheme, using the m3h format, with rate constants determined from the experimental data (22-24°C; extracellular Ca2+ concentration [Ca2+](o) = 3 mM). The T-type Ca2+ current inactivates rapidly during maintained depolarization (time constant, τ(h) ≃ 20 ms at -20 mV), yet recovery from inactivation is slow (time constant, τ(r) ≃ 270 ms at -80 mV). To reconcile these observations, a two-step kinetic scheme is proposed for the inactivation gate. Each of the time constants in this scheme is voltage dependent, with a maximum at about -85 mV ...
The T-type Ca2+ channel Cav3.2 is expressed in nociceptive and mechanosensitive sensory neurons. The mechanosensitive D-hair (down-hair) neurons, which innervate hair follicles, are characterized by a large-amplitude Cav3.2 T-current involved in the amplification of slow-moving stimuli. The molecules and signalling pathways that regulate T-current expression in mechanoreceptors are unknown. In the present study, we investigated the effects of NT-4 (neurotrophin-4) on Cav3.2 T-current expression in D-hair neurons in vitro. Interruption of the supply of NT-4 with peripheral nerve axotomy induced a non-transcriptional decrease in the T-current amplitude of fluorogold-labelled axotomized sensory neurons. The T-current amplitude was restored by incubation with NT-4. Deletion of NT-4 through genetic ablation resulted in a similar selective loss of the large-amplitude T-current in NT-4−/− sensory neurons, which was rescued by the addition of NT-4. NT-4 had no effect on the T-current in ...
They found that neurons showed an increase in viability after treatment with either L-type or T-type calcium channel inhibitors. Furthermore, neurons in the long-term and short-term cultures were protected, respectively, by L-type and T-type calcium channel blockers, suggesting that more than one calcium-signaling mechanism exists to regulate long- and short-term neuron survival.. There are presently no effective medications for age-related neurodegeneration. Bao said Our data provides implications for the use of this family of anti-epileptic drugs in developing new treatments for neuronal injury, and for the need of further studies of the use of such drugs in age-related neurodegenerative disorders.. 1. Neuroprotective effects of blockers for T-type calcium channels ...
The aim of this study was to use an established thalamocortical computer model to determine how T-type calcium channels work in concert with cortical excitability to contribute to pathogenesis and treatment response in CAE. METHODS: The model is comprised of cortical pyramidal, cortical inhibitory, thalamocortical relay, and thalamic reticular single-compartment neurons, implemented with Hodgkin-Huxley model ion channels and connected by AMPA, GABAA , and GABAB synapses. Network behavior was simulated for different combinations of T-type calcium channel conductance, inactivation time, steady state activation/inactivation shift, and cortical GABAA conductance. RESULTS: Decreasing cortical GABAA conductance and increasing T-type calcium channel conductance converted spindle to spike and wave oscillations; smaller changes were required if both were changed in concert. In contrast, left shift of steady state voltage activation/inactivation did not lead to spike and wave oscillations, whereas right ...
Despite a growing body of evidence implicating T-channels in nociception (Todorovic et al., 2001; Bourinet et al., 2005; Choi et al., 2007), the cellular and molecular basis of their function in nociceptors is poorly understood. In the present study, we demonstrated that reducing agents sensitize nociceptors both in vitro and in vivo in a manner that is dependent on Cav3.2. In current-clamp experiments on acutely dissociated rat DRG neurons, we show that l-cys lowers the threshold for excitability in C-type cells that express Cav3.2 currents but not in C-type cells expressing only HVA Ca2+ currents. Furthermore, we show that a similar form of sensitization is present in Cav3.2 current-containing, C-type nociceptors from wild-type mice but not from Cav3.2−/− mice. Additionally, we demonstrated that reducing agents induce thermal sensitization when injected into peripheral receptive fields in vivo, in which putative Cav3.2 channels are located on nociceptor endings. Importantly, this ...
Despite a growing body of evidence implicating T-channels in nociception (Todorovic et al., 2001; Bourinet et al., 2005; Choi et al., 2007), the cellular and molecular basis of their function in nociceptors is poorly understood. In the present study, we demonstrated that reducing agents sensitize nociceptors both in vitro and in vivo in a manner that is dependent on Cav3.2. In current-clamp experiments on acutely dissociated rat DRG neurons, we show that l-cys lowers the threshold for excitability in C-type cells that express Cav3.2 currents but not in C-type cells expressing only HVA Ca2+ currents. Furthermore, we show that a similar form of sensitization is present in Cav3.2 current-containing, C-type nociceptors from wild-type mice but not from Cav3.2−/− mice. Additionally, we demonstrated that reducing agents induce thermal sensitization when injected into peripheral receptive fields in vivo, in which putative Cav3.2 channels are located on nociceptor endings. Importantly, this ...
T-type Ca2+ channels are a distinct family of low voltage-activated Ca2+ channels which serve many roles in different tissues. Several studies have implicated them, for example, in the adaptive responses to chronic hypoxia in the cardiovascular and endocrine systems. Hydrogen sulfide (H2S) was more recently discovered as an important signalling molecule involved in many functions, including O2 sensing. Since ion channels are emerging as an important family of target proteins for modulation by H2S, and both T-type Ca2+ channels and H2S are involved in cellular responses to hypoxia, we have investigated whether recombinant and native T-type Ca2+ channels are a target for modulation by H2S. Using patch-clamp electrophysiology, we demonstrate that the H2S donor, NaHS, selectively inhibits Cav3.2 T-type Ca2+ channels heterologously expressed in HEK293 cells, whilst Cav3.1 and Cav3.3 channels were unaffected. Sensitivity of Cav3.2 channels to H2S required the presence of the redox-sensitive ...
Lunardi N, Ori C, Erisir A, Jevtovic-Todorovic V. General anesthesia causes long-lasting disturbances in the ultrastructural properties of developing synapses in young rats. Neurotoxicology Research 2010;17:179-88.. Messinger RB, Naik AK, Jagodic MM, Nelson MT, Lee WY, Choe WJ, Orestes P, Latham JR, Todorovic SM, Jevtovic-Todorovic V. In vivo silencing of the Ca(V)3.2 T-type calcium channels in sensory neurons alleviates hyperalgesia in rats with streptozocin-induced diabetic neuropathy. Pain 2009;145:184-95.. Latham JR, Pathirathna S, Jagodic MM, Levin ME, Nelson MT, Lee WY, Krishnan K, Covey DF, Todorovic SM, Jevtovic-Todorovic V. Selective T-type calcium channel blockade alleviates hyperalgesia of morbid-obesity-induced diabetic neuropathy in ob/ob mice. Diabetes 2009;58:2656-65.. Rizzi S, Carter LB, Ori C, Jevtovic-Todorovic V. Clinical anesthesia causes permanent damage to the fetal guinea pig brain. Brain Pathology 2008;18(2):198-210.. Yon, J-H, Carter LB, Reiter RJ, Jevtovic-Todorovic V. ...
The voltage-activated T-type calcium channel (CaV3.2) and the G protein-coupled neurokinin 1 (NK1) receptor are expressed in peripheral tissues and in central neurons where they participate in diverse physiological processes including neurogenic inflammation and nociception. In the present report, we demonstrate that recombinant CaV3.2 channels are reversibly inhibited by NK1 receptors when both proteins are transiently coexpressed in human embryonic kidney (HEK293) cells. We found that the voltage-dependent macroscopic properties of CaV3.2 currents were unaffected during NK1 receptor-mediated inhibition. However, inhibition was attenuated in cells coexpressing either the dominant-negative Gαq Q209L/D277N or the regulator of G protein signaling proteins 2 (RGS2) and 3T (RGS3T) which are effective antagonist of Gαq/11. By contrast, inhibition was unaffected in cells coexpressing human rod transducin (Gαt), which buffers Gβγ. Channel inhibition was blocked by U73122 and bisindolylmaleimide I, ...
NMP-7 is a drug which acts as both a non-selective agonist of the CB1 and CB2 cannabinoid receptors, and also as a blocker of T-type calcium channels, the target of anticonvulsant drugs such as ethosuximide. NMP-7 has an agonist EC50 of 96.9nM at CB1 and 10.5nM at CB2, and an IC50 of 1.84μM for blocking Cav3.2 T-type calcium channels. In animal studies it produces potent analgesic effects in a variety of different tests.[1] ...
Local signals maintain mature stem cells in lots of tissues. differentiated somatic cells in the adult mammalian testis but its rules isnt well realized. Our work shows that sex maintenance happens in adult somatic stem cells and that highly conserved procedure can be governed by effectors of market signals. Introduction Man versus female destiny is managed by a number of systems across taxa (Kopp 2012 In mammals this choice was lately found to become labile actually in adults; lack of sex-specific transcriptional regulators in the adult mouse gonad causes differentiated somatic cells to transdifferentiate into somatic cells of the contrary sex Resveratrol (Matson et al. 2011 Uhlenhaut et al. 2009 This means that that sexual identification must continuously become maintained in particular differentiated cell types lengthy after sex dedication has happened. Whether sexual identification is plastic material in undifferentiated adult stem cells continues to be unfamiliar. Since adult stem cells ...
Codon 141 in Ovine PRNP Gene Modulates Incubation Time in Sheep Orally Infected with BSE Boon Chin Tan Anthony R. modulating incubation time in sheep infected by this route. To investigate this we orally infected 39 sheep (ARQ/ARQ) which were polymorphic for either leucine (L) or phenylalanine (F) at codon 141 with BSE. The current incubation period for sheep confirmed as having BSE ranged greatly. However when we analyzed the incubation period (IP) as a function of the polymorphism at codon 141 we found statistical differences between the amino acid variant and the incubation time (p < 0.0001 for LL(141)/FF(141) and LL(141)/LF(141)). Sheep homozygote for LL(141) showed the shortest IP whereas LF(141) exhibited the longest IP and FF(141) had intermediate IPs. We are undertaking further genotypic analysis and cell free conversion assays to understand the mechanisms behind this varied response to infection. For this first time using this model we show that the amino acid at codon 141 modulate the ...
Using the video imaging technique this group has previously reported that regulatory volume decrease (RVD) in ZR-75-1 cells is Ca2+ dependent. RVD was inhibited in the absence of external Ca2+ and in the presence of voltage-gated Ca2+ channel inhibitors, nifedipine (L-type) and flunarizine (T-type; Ashes et al. 2002). These results suggested that external Ca2+ entered the cell via voltage-gated L- and/or T-type Ca2+ channels. In this study, the expression of L- and T-type channels was investigated in ZR-75-1 cells using reverse transcriptase-polymerase chain reaction (RT-PCR). The α1C and α1D are subunits of the L-type Ca2+ channel. The α1C subunit is expressed in cardiac muscle and the α1D subunit in the CNS and endocrine cells, where it may have a role in stimulus-secretion coupling. The α1G, α1H and α1I subunits have been cloned and display biophysical and pharmacological properties of native T-type Ca2+ channels when overexpressed in Xenopus oocytes or HEK-293 cells (Randall & Benham ...
Amiloride hydrochloride hydrate (N-Amidino-3,5-diamino-6-chloropyrazinecarboxamide);≥98% HPLC, powder; Amiloride is a selective T-type calcium channel blocker, an epithelial sodium channel blocker and a selective inhibitor of urokinase plasminogen activator (uPA); Selective T-type Ca2+
T-type channels are distinguished from high voltage-activated (HVA)1 Ca2+ channels by their unique biophysical properties, including low voltage activation, fast activation and inactivation kinetics that produce a criss-crossing pattern between successive traces of a current-voltage (IV) protocol, slow deactivation kinetics, and tiny single channel conductance (Perez-Reyes [528], Armstrong [1237], Carbone [1238], Randall [340]).. Expression studies found that Cav3.3 channels generate currents with much slower activation and inactivation kinetics than Cav3.1 and Cav3.2 channels, which show the more typical transient kinetics described for native T-type channels (Perez-Reyes [528], Perez-Reyes [1239], Cribbs [1240], Lee [1241]).. Cav3.1 and Cav3.2 channels are activating and inactivating much faster than Cav3.3 channels. (Park [113]). The kinetics of T-type channels resemble those of Na+ channels, albeit on a slower time scale, suggesting that they may also inactivate by a ball-and-chain ...
Numerous investigations reported that increases of internal Ca2+ (Ca2+i) pivotally regulate high voltage-activated (HVA) Ca2+ channels via calmodulin (CaM). However, it is largely elusive that Ca2+i can regulate low voltage-activated T-type Ca2+ channels. Using whole cell patch clamp, we compared the biophysical properties of Ca2+ current through T-type Ca2+ channel Cav3.1, Cav3.2, or Cav3.3 stably expressed in HEK293 cells between internal solutions containing 27 nM and l μM free Ca2+. Both activation and inactivation kinetics of Cav3.3 current in l μM Ca2+i solution were more rapid than those of Cav3.3 in 27 nM Ca2+i solution. In addition, both activation and steady-state inactivation curves of Cav3.3 were negatively shifted in the higher Ca2+i solution. In contrast, the biophysical properties of Cav3.1 and Cav3.2 isoforms were not different between the two internal solutions. Overexpression of CaM1234 (calmodulin mutant lacking 4 Ca2+ binding sites) strongly suppressed the effects of l μM ...
This gene encodes the pore-forming alpha subunit of a voltage gated calcium channel. The encoded protein is a member of a subfamily of calcium channels referred to as is a low voltage-activated, T-type, calcium channel. The channel encoded by this protein is characterized by a slower activation and inactivation compared to other T-type calcium channels. This protein may be involved in calcium signaling in neurons. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]
Glioblastoma (GBM) stem-like cells (GSC) promote tumor initiation, progression, and therapeutic resistance. Here, we show how GSCs can be targeted by the FDA-approved drug mibefradil, which inhibits the T-type calcium channel Cav3.2. This calcium channel was highly expressed in human GBM specimens and enriched in GSCs. Analyses of the The Cancer Genome Atlas and REMBRANDT databases confirmed upregulation of Cav3.2 in a subset of tumors and showed that overexpression associated with worse prognosis. Mibefradil treatment or RNAi-mediated attenuation of Cav3.2 was sufficient to inhibit the growth, survival, and stemness of GSCs and also sensitized them to temozolomide chemotherapy. Proteomic and transcriptomic analyses revealed that Cav3.2 inhibition altered cancer signaling pathways and gene transcription. Cav3.2 inhibition suppressed GSC growth in part by inhibiting prosurvival AKT/mTOR pathways and stimulating proapoptotic survivin and BAX pathways. Furthermore, Cav3.2 inhibition decreased ...
TY - JOUR. T1 - Cannabis, psychosis and the thalamus. T2 - A theoretical review. AU - Vukadinovic, Zoran. AU - Herman, Merrill S.. AU - Rosenzweig, Ivana. PY - 2013/5/1. Y1 - 2013/5/1. N2 - The role of cannabis in the etiology of schizophrenia has been documented as possibly the strongest environmental risk factor. However, the pathomechanism whereby cannabis use increases this risk has not yet been identified. We argue that this pathomechanism may involve direct effects of exogenous cannabinoids on T-type calcium channels in the thalamus. These channels are crucial for amplification of corticothalamic inputs, as well as for the ability of the thalamus to generate neuronal burst firing. Cortically induced thalamic burst firing has been found to be important in trans-thalamic cortico-cortical interactions. Therefore, any potential interference with the burst firing mode in the thalamus could lead to an impairment in these interactions, which in turn causes a relative disconnection between ...
Calcium and ion channels play a critical role in neuronal signaling. T-type calcium channels (Cav3.1, 3.2, & 3.3) respond to small membrane depolarizations and gate the activity of additional ion channels whose activation results in the firing of neurons. Cav3s finely-tuned voltage-gated property and pacemaker function mediates the transition from tonic to bust-firing and generates neural oscillations between brain nuclei and across their pathways.. The transition to burst-firing and abnormal oscillatory pattern occurs in a number of neurologic disorders, including essential tremor, Parkinsons disease, dystonia, epilepsy, pain, and schizophrenia and rare, pediatric genetic disorders, such as Angelman Syndrome. These diseases are mediated by Cav3, a common pathophysiologic pathway. Central and peripheral biomarkers facilitate in vivo readouts of dysrhythmia s and target modulation with Cavions Cav3 therapies.. Despite substantial interest in Cav3 as a target, to date there has been little ...
Comments: T-type calcium channel with high threshold for activation, used in somatic and dendritic regions, calculates i_ca using channel permeability instead of conductance. Adapted from magee and johnston (1995), modified to account for ca2+ spikes. No model db ancestors. This is a modeling study, and the animal model is considered to be rat. The authors compare the model to experimental results mostly in rats (e.g. Magee 1998, spruston et al. 1995) and the morphology used is also from rat (2 months old, cannon et al. 1998, n123). Channel kinetics come from various sources ...
TITLE T-calcium channel : T-type calcium channel for Mala Shah UNITS { (mA) = (milliamp) (mV) = (millivolt) (molar) = (1/liter) (mM) = (millimolar) FARADAY = 96520 (coul) R = 8.3134 (joule/degC) KTOMV = .0853 (mV/degC) } PARAMETER { v (mV) celsius = 25 (degC) gcatbar=.003 (mho/cm2) cai = 50.e-6 (mM) cao = 2 (mM) q10 = 5 mmin=0.2 hmin=10 a0h =0.015 zetah = 3.5 vhalfh = -75 gmh=0.6 a0m =0.04 zetam = 2 vhalfm = -28 gmm=0.61 vhm=-60 vhh=-85 } NEURON { SUFFIX cat USEION ca READ cai,cao WRITE ica RANGE gcatbar, ica, gcat GLOBAL hinf,minf,mtau,htau } STATE { m h } ASSIGNED { ica (mA/cm2) gcat (mho/cm2) hinf htau minf mtau } INITIAL { rates(v) m = minf h = hinf } BREAKPOINT { SOLVE states METHOD cnexp gcat = gcatbar*m*m*h ica = gcat*ghk(v,cai,cao) } DERIVATIVE states { : exact when v held constant rates(v) m = (minf - m)/mtau h = (hinf - h)/htau } FUNCTION ghk(v(mV), ci(mM), co(mM)) (mV) { LOCAL nu,f f = KTF(celsius)/2 nu = v/f ghk=-f*(1. - (ci/co)*exp(nu))*efun(nu) } FUNCTION KTF(celsius (DegC)) (mV) ...
Choe W, Messinger RB, Leach E, Eckle VS, Obradovic A, Salajegheh R, Jevtovic-Todorovic V, Todorovic SM. TTA-P2 is a potent and selective blocker of T-type calcium channels in rat sensory neurons and a novel antinociceptive agent. Mol Pharmacol. 2011;80:900-10 ...
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Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown. However, using cell-based assays and integrated proteomics, phosphoproteomics, and transcriptomics analyses, we identified the downstream signaling events these drugs affect. Changes in plasma membrane depolarization and elevated intracellular Na+, which compromised Na+-dependent nutrient transport, were documented. Deficits in nutrient deficit acted in turn to trigger the unfolded protein response and the amino acid response, leading ultimately to nutrient starvation and GIC cell death. ...
DePuy SD, Yao J, Hu C, McIntire W, Bidaud I, Lory P, Rastinejad F, Gonzalez C, Garrison JC, Barrett PQ. The molecular basis for T-type Ca2+ channel inhibition by G protein beta2gamma2 subunits. Proc Natl Acad Sci U S A. 2006 Sep 26; 103(39):14590-5 ...
Participation of low-threshold calcium spikes in excitatory synaptic transmission in guinea pig medial frontal cortex.: We studied the activation of low-thresho
Regulation of low-voltage activated T-type Ca2+ channel activity by kinases and heterotrimeric G-proteins and their roles in physiological responses.. ...
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Ca2+ influx through voltage-dependent Ca2+ channels regulates vascular remodeling and contraction. However, the role of T-type Ca2+ channels (TCCs) has remained unknown in the ductus arteriosus (DA). Here we hypothesized that Ca2+ influx via TCC contributed to DA closure through promoting neointimal cushion formation and oxygen-induced vascular contraction. Quantitative RT-PCR analysis revealed that α1G, a TCC subtype, was significantly up-regulated in rat neonatal DA tissues at birth and in DA smooth muscle cells (SMCs) that were exposed to oxygen. The expression of α1G mRNA was higher in DA than in the aorta. Immunohistlogical analysis revealed that α1G was localized predominantly to the region of intimal thickening in fetal DA at term and to the central core of neonatal DA at birth. To examine the effects of blockade of TCCs, we used α1G-specific siRNA or R(−)-efonidipine, a highly selective TCC blocker that was recently developed. α1G-specific siRNAs inhibited SMC migration by 55% ...
L-type calcium channel blockers are used to treat hypertension. In most areas of the body, depolarization is mediated by sodium influx into a cell; changing the calcium permeability has little effect on action potentials. However, in many smooth muscle tissues, depolarization is mediated primarily by calcium influx into the cell. L-type calcium channel blockers selectively inhibit these action potentials in smooth muscle which leads to dilation of blood vessels; this in turn corrects hypertension.[8]. T-type calcium channel blockers are used to treat epilepsy. Increased calcium conductance in the neurons leads to increased depolarization and excitability. This leads to a greater predisposition to epileptic episodes. Calcium channel blockers reduce the neuronal calcium conductance and reduce the likelihood of experiencing epileptic attacks.[9]. ...
The present study provides 2 major new findings. First, in contrast to its peripheral effects, centrally administered nifedipine decreases RSNA and HR in conscious SHR. Second, these sympathoinhibitory effects of nifedipine are enhanced in SHR on high versus regular sodium intake.. Dihydropyridine-sensitive, low-voltage-activated calcium channels have been demonstrated in rat brain neurons freshly isolated from regions such as the ventromedial hypothalamus.6 The role of the different types of calcium channels in neuronal synaptic transmission has not been clarified. In rat hippocampal cells,7 during neuronal activation postsynaptic or presynaptic Ca2+ entry involves the activation of the P/Q-, L-, or N-type Ca2+ channels but not the T-type Ca2+ channels. Unless dissolved in certain solvents such as dimethylsulfoxide,15 nifedipine blocks only L-type channels and has no effects on T-type channels in neuronal cells.8 15 In the present study nifedipine was dissolved in a vehicle containing no ...
Frequency of genetic polymorphism of calcium channels gene CACNA1C in healthy individuals and patients with arterial hypertension
When neuronal activity is reduced over a period of days, compensatory changes in synaptic strength and/or cellular excitability are triggered, which are thought to act in a manner to homeostatically recover normal activity levels. The time course over which changes in homeostatic synaptic strength and cellular excitability occur are not clear. Although many studies show that 1-2 days of activity block are necessary to trigger increases in excitatory quantal strength, few studies have been able to examine whether these mechanisms actually underlie recovery of network activity. Here, we examine the mechanisms underlying recovery of embryonic motor activity following block of either excitatory GABAergic or glutamatergic inputs in vivo. We find that GABAA receptor blockade triggers fast changes in cellular excitability that occur during the recovery of activity but before changes in synaptic scaling. This increase in cellular excitability is mediated in part by an increase in sodium currents and a reduction
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The combination of the nonspecific F-type channels and the closing of K+ channels results in a steady depolarization when membrane potential is negative, these channels paired with the effects of T-type Ca+2 channels allow recurring depolarization following repolarization and therefore facilitate the pacemaker ...
Abstract: We present a search for electroweak production of single top quarks in the electron+jets and muon+jets decay channels. The measurements use ~90 pb^-1 of data from Run 1 of the Fermilab Tevatron collider, collected at 1.8 TeV with the DZero detector between 1992 and 1995. We use events that include a tagging muon, implying the presence of a b jet, to set an upper limit at the 95% confidence level on the cross section for the s-channel process ppbar-,tb+X of 39 pb. The upper limit for the t-channel process ppbar-,tqb+X is 58 pb ...
Analysis of the Wtb vertex from the measurement of triple-differential angular decay rates of single top quarks produced in the t-channel at $\sqrt{s}=8$ TeV with the ATLAS detector / M. Aaboud, [et al.], L. ADAMCZYK, [et al.], T. BOŁD, [et al.], W. DĄBROWSKI, [et al.], G. P. GACH, [et al.], I. GRABOWSKA-BOŁD, [et al.], M. P. GUZIK, [et al.], P. A. JANUS, [et al.], D. KISIELEWSKA, [et al.], S. KOPERNY, [et al.], T. Z. KOWALSKI, [et al.], J. A. KREMER, [et al.], B. MINDUR, [et al.], M. PRZYBYCIEŃ, [et al.], A. ZEMŁA, [et al.] // The Journal of High Energy Physics ; ISSN 1126-6708. - 2017 iss. 12 art. no. 017, s. [1], 1-59. - Bibliogr. s. 37-42, Abstr.. - Publikacja dostępna online od: 2017-12-04. - tekst: https://goo.gl/XXSNDX ...
A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous as voltage-gated calcium channel, although there are also ligand-gated calcium channels. The following tables explain gating, gene, location and function of different types of calcium channels, both voltage and ligand-gated. the receptor-operated calcium channels (in vasoconstriction) P2X receptors L-type calcium channel blockers are used to treat hypertension. In most areas of the body, depolarization is mediated by sodium influx into a cell; changing the calcium permeability has little effect on action potentials. However, in many smooth muscle tissues, depolarization is mediated primarily by calcium influx into the cell. L-type calcium channel blockers selectively inhibit these action potentials in smooth muscle which leads to dilation of blood vessels; this in turn corrects hypertension. T-type calcium channel blockers are used to treat epilepsy. Increased calcium conductance in ...
Injection of NMDAR antagonist into the thalamus can produce delta frequency EEG oscillations in the thalamocortical system. It is surprising that an antagonist of an excitatory neurotransmitter should trigger such activity, and the mechanism is unknown. One hypothesis is that the antagonist blocks excitation of GABAergic cells, thus producing disinhibition. To test this hypothesis, we investigated the effect of NMDAR antagonist (APV) on cells of the nucleus reticularis (nRT) in rat brain slices, a thalamic nucleus that can serve as a pacemaker for thalamocortical delta oscillations and that is composed entirely of GABAergic neurons. We found, unexpectedly, that nRT cells are hyperpolarized by APV. This occurs because these cells have an unusual form of NMDAR (probably NR2C) that contributes inward current at resting potential in response to ambient glutamate. The hyperpolarization produced by APV is sufficient to deinactivate T-type calcium channels, and these trigger rhythmic bursting at delta
ID F7H6P3_MACMU Unreviewed; 2291 AA. AC F7H6P3; DT 27-JUL-2011, integrated into UniProtKB/TrEMBL. DT 30-NOV-2016, sequence version 2. DT 25-OCT-2017, entry version 36. DE RecName: Full=Voltage-dependent T-type calcium channel subunit alpha {ECO:0000256,RuleBase:RU003808}; GN Name=CACNA1G {ECO:0000313,Ensembl:ENSMMUP00000034848}; OS Macaca mulatta (Rhesus macaque). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Cercopithecidae; Cercopithecinae; Macaca. OX NCBI_TaxID=9544 {ECO:0000313,Ensembl:ENSMMUP00000034848, ECO:0000313,Proteomes:UP000006718}; RN [1] {ECO:0000313,Ensembl:ENSMMUP00000034848, ECO:0000313,Proteomes:UP000006718} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=17573 {ECO:0000313,Ensembl:ENSMMUP00000034848, RC ECO:0000313,Proteomes:UP000006718}; RX PubMed=17431167; DOI=10.1126/science.1139247; RA Gibbs R.A., Rogers J., Katze M.G., Bumgarner R., Weinstock G.M., RA Mardis ...
ID I3N0U5_ICTTR Unreviewed; 1770 AA. AC I3N0U5; DT 11-JUL-2012, integrated into UniProtKB/TrEMBL. DT 11-JUL-2012, sequence version 1. DT 27-SEP-2017, entry version 37. DE RecName: Full=Voltage-dependent T-type calcium channel subunit alpha {ECO:0000256,RuleBase:RU003808}; GN Name=CACNA1I {ECO:0000313,Ensembl:ENSSTOP00000017991}; OS Ictidomys tridecemlineatus (Thirteen-lined ground squirrel) OS (Spermophilus tridecemlineatus). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciuromorpha; OC Sciuridae; Xerinae; Marmotini; Ictidomys. OX NCBI_TaxID=43179 {ECO:0000313,Ensembl:ENSSTOP00000017991, ECO:0000313,Proteomes:UP000005215}; RN [1] {ECO:0000313,Ensembl:ENSSTOP00000017991} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RG The Broad Institute Genome Assembly & Analysis Group; RG Computational R&D Group; RG and Sequencing Platform; RA Di Palma F., Alfoldi J., Johnson J., Berlin A., Gnerre S., Jaffe D., RA MacCallum ...
학술회의] 민철기, Hae-Kwon Kim, Jae-Ho Lee, Yun-Jin Jung, Kyoo Wan Choi, Seung-Jae Lee, Sung Eun Lee, Hwa Lee Ryu, Ju-Hee Lee, Inhibitory action of mibefradil on steroidogenesis in mouse leydig cells: involvement of Ca+2 entry through T-type Ca+2 channels in steroidogenesis , ESHRE 21st Annual Meeting , Vol.21 , pp.121 -121 (Jun, 2005) ...
Joksovic PM, Brimelow BC, Murbartián J, Perez-Reyes E, Todorovic SM. Contrasting anesthetic sensitivities of T-type Ca2+ channels of reticular thalamic neurons and recombinant Ca(v)3.3 channels. Br J Pharmacol. 2005 Jan; 144(1):59-70 ...
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Is this supported? Id like to pass calcium ion concentration info of astrocytes to neighboring pyramidal cells. ... to the neighboring pyramidal cells and interneurons via point process synapses that inhibit and excite the two types describing ... then have another mechanism in the affected neuron sections that uses that concentration to modulate channel conductances or ... What are you trying to represent? Calcium-dependent release of neurotransmitters or other substances from astrocytes? Effects ...
Is this supported? Id like to pass calcium ion concentration info of astrocytes to neighboring pyramidal cells. ... to the neighboring pyramidal cells and interneurons via point process synapses that inhibit and excite the two types describing ... then have another mechanism in the affected neuron sections that uses that concentration to modulate channel conductances or ... What are you trying to represent? Calcium-dependent release of neurotransmitters or other substances from astrocytes? Effects ...
You have a prosthesis? What type? I had a St. Jude aortic installed in August of 1990. IIRC, the hospital bill was $60K. That ... that one in dec 89 had a new anti-calcium treatment, supposed to last longer without needing replacement. and its made of cow ... hospital food was most excellent, but the 5 channels of bollywood musicals on the talking box was ungroovy.. total bill ... You have a prosthesis? What type? I had a St. Jude aortic installed in August of 1990. IIRC, the hospital bill was $60K. That ...
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CHANNELS = [in0/ref, in1/ref, in2/ref] import platform try: import winsound type=windows except: import os type=other ... CHARGING SYSTEM CALCIUM MODE", bold, 159)) print(fg(" WARNING CALCIUM MODE",bold, 9)) # bus.write_byte_data(DEVICE_ADDR, 2 ... for channel in CHANNELS: value = ads1015.get_compensated_voltage(channel=channel, reference_voltage=reference) if channel == ... for channel in CHANNELS: value = ads1015.get_compensated_voltage(channel=channel, reference_voltage=reference) if channel == ...
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  • 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)
  • The T-type channel is regulated by both dopamine and other neurotransmitters, which inhibit T-type currents. (wikipedia.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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)

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