Calcium Channels: 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.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Calcium Channels, L-Type: 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.Ion Channels: 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, N-Type: CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.Calcium Channels, T-Type: 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.Calcium Signaling: 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.Calcium Channel Agonists: 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.Ion Channel Gating: 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, Inwardly Rectifying: Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.Calcium Channels, P-Type: CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.Calcium Channels, Q-Type: CALCIUM CHANNELS located in the neurons of the brain.Dihydropyridines: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.Calcium Channels, R-Type: CALCIUM CHANNELS located in the neurons of the brain. They are inhibited by the marine snail toxin, omega conotoxin MVIIC.Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.Potassium Channel Blockers: 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.Chloride Channels: Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.omega-Conotoxin GVIA: 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.Electrophysiology: 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, Dietary: 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.Membrane Potentials: 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).omega-Conotoxins: 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 Channels, Voltage-Gated: 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.Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.KATP Channels: 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.Calcium: 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.Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent.Isradipine: 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.Patch-Clamp Techniques: 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, Calcium-Activated: Potassium channels whose activation is dependent on intracellular calcium concentrations.Nitrendipine: 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.Mibefradil: A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE.Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.Sodium Channel Blockers: 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.Barium: 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.Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.omega-Agatoxin IVA: 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.TRPC Cation Channels: 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.Shaker Superfamily of Potassium Channels: 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.Kinetics: The rate dynamics in chemical or physical systems.Neurons: 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, Cultured: 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.Large-Conductance Calcium-Activated Potassium Channels: 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.Potassium: 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.Calcium Carbonate: 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.Cyclic Nucleotide-Gated Cation Channels: 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.Oocytes: 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).Molecular Sequence Data: 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.Calcium Chloride: A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning.Rats, Sprague-Dawley: 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.TRPV Cation Channels: 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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Nicardipine: 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.Xenopus laevis: 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.Amino Acid Sequence: 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.Ryanodine Receptor Calcium Release Channel: 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.TRPM Cation Channels: 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.Acid Sensing Ion Channels: 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.Spider Venoms: 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 Phosphates: Calcium salts of phosphoric acid. These compounds are frequently used as calcium supplements.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Epithelial Sodium Channels: 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.Kv1.3 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.Ether-A-Go-Go Potassium Channels: 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.Calcium Isotopes: 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.Kv1.2 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.Kv1.1 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.Calcium Radioisotopes: 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.Protein Subunits: 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.Amlodipine: A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of ANGINA PECTORIS and HYPERTENSION.Kv1.5 Potassium Channel: 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.Agatoxins: A class of polyamine and peptide toxins which are isolated from the venom of spiders such as Agelenopsis aperta.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Myocardium: 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.Small-Conductance Calcium-Activated Potassium Channels: 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.Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Rabbits: 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.Ion Transport: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Adenosine Triphosphate: 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.Mollusk Venoms: 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.Transient Receptor Potential Channels: 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.KCNQ Potassium Channels: 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.Shab Potassium Channels: 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.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.KCNQ1 Potassium Channel: A voltage-gated potassium channel that is expressed primarily in the HEART.Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Shaw Potassium Channels: A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.Kv1.4 Potassium Channel: A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.Tetrodotoxin: 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.Protein Structure, Tertiary: 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.Models, Biological: 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.Calcium Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi.Mutation: 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.Chelating Agents: Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS.Gallopamil: Coronary vasodilator that is an analog of iproveratril (VERAPAMIL) with one more methoxy group on the benzene ring.G Protein-Coupled Inwardly-Rectifying Potassium Channels: 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.Calcium Gluconate: The calcium salt of gluconic acid. The compound has a variety of uses, including its use as a calcium replenisher in hypocalcemic states.Shal Potassium Channels: 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.Presynaptic Terminals: 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.Magnesium: 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.Fura-2: A fluorescent calcium chelating agent which is used to study intracellular calcium in tissues.Peptides: 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.Thapsigargin: A sesquiterpene lactone found in roots of THAPSIA. It inhibits CA(2+)-TRANSPORTING ATPASE mediated uptake of CALCIUM into SARCOPLASMIC RETICULUM.Heart: The hollow, muscular organ that maintains the circulation of the blood.KCNQ2 Potassium Channel: A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: 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.Transfection: 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.Guinea Pigs: 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.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Tetraethylammonium: A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme UREASE.Neurotransmitter Agents: 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.Biophysics: The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.Signal Transduction: 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: 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.Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to CADMIUM POISONING.Scorpion Venoms: 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.Muscles: Contractile tissue that produces movement in animals.Nisoldipine: 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.NAV1.5 Voltage-Gated Sodium Channel: 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.Hippocampus: 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, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Intermediate-Conductance Calcium-Activated Potassium Channels: 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.Membrane Proteins: 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.Synaptic Transmission: 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.KCNQ3 Potassium Channel: 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.Large-Conductance Calcium-Activated Potassium Channel alpha Subunits: The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.Ions: 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.Ganglia, Spinal: 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.Hydrogen-Ion Concentration: 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)Cations: Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.Nerve Tissue ProteinsInositol 1,4,5-Trisphosphate Receptors: 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.Protein Binding: 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.Muscle Contraction: 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.Ryanodine: 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.Delayed Rectifier Potassium Channels: 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.Calmodulin: 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, Messenger: 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.NAV1.2 Voltage-Gated Sodium Channel: 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.Voltage-Gated Sodium Channels: 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.Chlorides: Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.Myocytes, Cardiac: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.Charybdotoxin: A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.OxadiazolesLipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.Biophysical Phenomena: The physical characteristics and processes of biological systems.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Intracellular Fluid: The fluid inside CELLS.Animals, Newborn: Refers to animals in the period of time just after birth.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Strontium: An element of the alkaline earth family of metals. It has the atomic symbol Sr, atomic number 38, and atomic weight 87.62.Flunarizine: 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.Calcimycin: 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.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.GTP-Binding Proteins: 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.-.Protein Conformation: 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).Fluorescent Dyes: 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.Calcium Compounds: Inorganic compounds that contain calcium as an integral part of the molecule.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.4-Aminopyridine: 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.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Cyclic AMP: 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.Synapses: 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.Cations, Divalent: Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis.Apamin: 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.Protein Kinase C: 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.Structure-Activity Relationship: 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.Cyclic AMP-Dependent Protein Kinases: 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.Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.Potassium Chloride: 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.Caffeine: 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.Receptors, Drug: 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.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Felodipine: 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.Antihypertensive Agents: 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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Sulfonylurea Receptors: 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.Muscle, Smooth: 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)Cerebellum: 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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Sarcolemma: The excitable plasma membrane of a muscle cell. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Brain: 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.NAV1.4 Voltage-Gated Sodium Channel: 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.Voltage-Dependent Anion Channels: 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.Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.Extracellular Space: 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.Dogs: 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)Azetidinecarboxylic Acid: A proline analog that acts as a stoichiometric replacement of proline. It causes the production of abnormal proteins with impaired biological activity.Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.Mice, Inbred C57BLReceptors, Nicotinic: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The regulation of transmitter release at the neuromuscular junction is tightly regulated by the influx of calcium in the presynaptic nerve terminal. Interestingly, the probability that release sites at the neuromuscular junction will liberate transmitter during each action potential is very low. The reasons for this low probability of release are not well understood. To test the hypothesis that individual N-type calcium channels open with a low probability, single channel recordings of N-type voltage-gated calcium channels were performed. Using this approach I determined the conductance of these channels, their probability of gating during an action potential waveform, and the magnitude of calcium flux during a single channel opening. I conclude from these studies that N-type voltage-gated calcium channels have a very low probability of opening (< 5%) during an action potential and the characteristics of calcium entry during single channel openings can help to explain the low probability of ...
N-type calcium channels are voltage gated calcium channels that are distributed throughout the entire body. These channels are high voltage activated channels composed of alpha-1B subunits. The alpha subunit forms the pore through which the calcium enters and helps to determine most of the channels properties. The alpha subunit is also known as the calcium channel/voltage dependent/N type, alpha 1 subunit (CACNA1B), or Cav2.2 which is used in therapeutic processes), which in humans is encoded by the CACNA1B gene. They also contain associated subunits such as β1, β3, β4, α2δ, and possibly γ. These channels are known for their importance in the nervous system. They play a small role in the migration of immature neurons before the establishment of their mature synapses, and they are critically involved in the release of neurotransmitters, which is also similar to another type of calcium channels, known as P-type calcium channels. N-type calcium channels are targets for the development of ...
N-Type Calcium Channels: CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.
We identified four properties that reduced N-channel Po at depolarized voltages. These properties were null sweeps, low Po gating, inactivation, and slow activation. Several of these gating processes behaved in a manner consistent with the modal hypothesis. In particular, null sweeps were significantly clustered in the majority of our single N-channel patches. Clustering of null records has been reported for L-type calcium channels (Hess et al., 1984), skeletal muscle sodium channels (Horn et al., 1994), and N-type calcium channels (Rittenhouse and Hess, 1994). These clustered null sweeps were interpreted to result from a gating mode from which the channel will not open. Such a mode could be represented by a long-lived inactivated state that had a mean dwell time lasting several sweep intervals (4-6 s in our recordings). Whole-cell recordings have demonstrated an inactivation process from which N-current is slow to recover (Jones and Marks, 1989b).. In three single N-channel patches, we observed ...
A set of fluorophenoxyanilides, designed to be simplified analogues of previously reported ω-conotoxin GVIA mimetics, were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or Cav2.2 channel is a validated target for the treatment of refractory chronic pain. Despite being significantly less complex than the originally designed mimetics, up to a seven-fold improvement in activity was observed.
Pain signaling involves transmission of nociceptive stimuli in the spinal cord where a critical balance between excitatory and inhibitory inputs determines the response to noxious stimuli. The neuropeptide, substance P (SP), mediates transmission of pain in part by binding to the tachykinin receptor (NK-1R) in the dorsal horn (DH) of the spinal cord. One of SPs downstream effects is to modulate N-type Ca2+ (N-) channels. While phospholipid breakdown is a part of the inflammatory process that accompanies tissue damage, the role of this metabolic pathway has not been completely described with respect to N-channel modulation during pain signaling. Despite the incomplete understanding of this modulation, pharmacological antagonists of both NK-1R and N-channels have been used to treat pain. In Chapter II, using whole-cell patch clamp recording techniques, the SP signaling cascade that mediates inhibition of recombinant N-channel activity was characterized. By adopting a pharmacological approach, I show that
TY - JOUR. T1 - Domain III regulates N-type (Ca V2.2) calcium channel closing kinetics. AU - Yarotskyy, Viktor. AU - Gao, Guofeng. AU - Peterson, Blaise Z.. AU - Elmslie, Keith S.. PY - 2012/4/1. Y1 - 2012/4/1. N2 - Ca V2.2 (N-type) and Ca V1.2 (L-type) calcium channels gate differently in response to membrane depolarization, which is critical to the unique physiological functions mediated by these channels. We wondered if the source for these differences could be identified. As a first step, we examined the effect of domain exchange between N-type and L-type channels on activationdeactivation kinetics, which were significantly different between these channels. Kinetic analysis of chimeric channels revealed N-channellike deactivation for all chimeric channels containing N-channel domain III, while activation appeared to be a more distributed function across domains. This led us to hypothesize that domain III was an important regulator of N-channel closing. This idea was further examined with ...
Neuromed Pharmaceuticals Ltd. and Merck & Co., Inc. announced that they have signed a research collaboration and license agreement to research, develop and commercialize novel compounds for the tr ...
TY - JOUR. T1 - Protein inhibition by microinjection and RNA-mediated interference in tissue culture cells. T2 - complementary approaches to study protein function.. AU - Stout, Jane R.. AU - Rizk, Rania S.. AU - Walczak, Claire. PY - 2009. Y1 - 2009. N2 - A major goal in cell biology is to understand the molecular mechanisms of the biological process under study, which requires functional information about the roles of individual proteins in the cell. For many non-genetic model organisms researchers have relied on the use of inhibitory reagents, such as antibodies that can be microinjected into cells. More recently, the advent of RNA-mediated interference (RNAi) has allowed scientists to knockdown individual proteins and to examine the consequences of the knockdown. In this chapter we present a comparison between microinjection of inhibitory reagents and RNAi for the analysis of protein function in mammalian tissue culture cells, providing both a description of the techniques as well as a ...
DMN2023UCB4 N-CHANNEL ENHANCEMENT MODE FIELD MOSFET Product Summary Features V(BR)DSS RSS(ON) Package 24V 26mΩ @ VGS = 4.5V X1-WLB1818-4     IS TA = +25°C 6.0A Built-in G-S Protection Diode Against ESD 2kV HBM Totally Lead-Free & Fully RoHS Compliant (Notes 1 & 2) Halogen and Antimony Free. "Green" Device (Note 3) Qualified to AEC-Q101 Standards for High Reliability Description This new generation MOSFET is designed to minimize the on-state resistance (RDS(ON)) with thin WLCSP packaging process and yet maintain superior switching performance, making it ideal for high efficiency power management applications. Mechanical Data    Case: X1-WLB1818-4 Moisture Sensitivity: Level 1 per J-STD-020 Terminal Connections: See Diagram Applications    Battery Management Load Switch Battery Protection X1-WLB1818-4 G1 G2 ESD PROTECTED TO 2kV N-Channel S1 Top View N-Channel S2 Equivalent Circuit Ordering Information (Note 4) Part Number DMN2023UCB4-7 Notes: Case X1-WLB1818-4 ...
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TY - JOUR. T1 - Further insights into the antinociceptive potential of a peptide disrupting the N-type calcium channel-CRMP-2 signaling complex. AU - Wilson, Sarah M.. AU - Brittain, Joel M.. AU - Piekarz, Andrew D.. AU - Ballard, Carrie J.. AU - Ripsch, Matthew S.. AU - Cummins, Theodore R.. AU - Hurley, Joyce H.. AU - Khanna, May. AU - Hammes, Nathan M.. AU - Samuels, Brian C.. AU - White, Fletcher A.. AU - Khanna, Rajesh. PY - 2011/1/1. Y1 - 2011/1/1. N2 - The N-type voltage-gated calcium channel (Ca v2.2) has gained immense prominence in the treatment of chronic pain. While decreased channel function is ultimately anti-nociceptive, directly targeting the channel can lead to multiple adverse side effects. Targeting modulators of channel activity may facilitate improved analgesic properties associated with channel block and a broader therapeutic window. A novel interaction between Ca v2.2 and collapsin response mediator protein 2 (CRMP-2) positively regulates channel function by increasing ...
Cilnidipine (INN) is a calcium channel blocker. It is a calcium antagonist accompanied with L-type and N-type calcium channel blocking functions. It was jointly developed by Fuji Viscera Pharmaceutical Company and Ajinomoto, and was approved to enter the market and be used as an anti-hypertensive in 1995.[citation needed] Unlike other calcium antagonists, cilnidipine can act on the N-type calcium channel in addition to acting on the L-type calcium channel. Cilnidipine is approved for use in Japan, China, India, Korea, and some European countries to treat hypertension. Cilnidipine decreases blood pressure and is used to treat hypertension and its comorbidities. Due to its blocking action at the N-type and L-type calcium channel, cilnidipine dilates both arterioles and venules, reducing the pressure in the capillary bed. Cilnidipine is vasoselective and has a weak direct dromotropic effect, a strong vasodepressor effect, and an arrhythmia-inhibiting effect. Blood pressure control with cilnidipine ...
L-type (CaV1.2) voltage-gated calcium channels play critical roles in membrane excitability, gene expression, cardiac and smooth muscle contraction. Alternative splicing enriches the functional diversity of the pore-forming CaV1.2 alpha-1 subunit. Systematic screening of the human CaV1.2 alpha-1 gene by the transcript-scanning method revealed 19 of the 55 exons were subjected to alternative splicing, and two of these were novel exons. A large IVS3-S4 variability resulting from combinatorial utilization of exons 31-33 demonstrated a correlation between increased IVS3-S4 linker length and more depolarized activation potentials.Sixty-four splicing profiles of CaV1.2 alpha-1 subunit were identified from 6 full-length cDNA libraries generated from heart and aortic tissues of the Spontaneously Hypertensive Rats and Wistar Kyoto Rats. The tissue-selective and pathologically induced splicing profiles of 10 alternatively spliced exons assessed indicated a striking alteration in exon utilization and ...
Among G-protein-coupled receptors, CB1Rs are unusual in that they are expressed nearly exclusively in presynaptic terminals and are excluded from the soma of adult neurons. This unique distribution pattern makes it difficult to directly examine the coupling of native CB1Rs to Ca2+ channels. Therefore heterologous expression of CB1Rs by intranuclear injection of CB1 cDNA in an isolated adult mammalian neuron that has well-studied G-protein pathways facilitates in situ investigation of CB1 receptors. In this neuronal expression system, we demonstrated that three putative endocannabinoids, AEA, 2-AG, and 2-AGE, like the cannabimimetic aminoalkylindole WIN, initiate PTX-sensitive, voltage-dependent N-type Ca2+ channel inhibition via CB1Rs.. WIN is a synthetic CB1R agonist widely used in the studies of CB1Rs, including DSI and DSE. Modulation of N-type Ca2+ channel by WIN via CB1Rs was first observed in differentiated NG108-15 neuroblastoma cells and N18 cells (Caulfield and Brown,1992; Mackie and ...
N-type calcium channels belong to the family of voltage gated calcium channels , which open in response to membrane depolarisation. These channels are responsible for the calcium influx that triggers neurotransmitter release at presynaptic terminals. N - type channels are particularly important in mediating neurotransmitter release at the presynaptic terminals of peripheral sensory neurons and have been implicated i n neuropathic pain. Understanding the regulation of N - type channels is critical to the development of treatments that target these channels. Until now it has been difficult to directly investigate the regulation of their expression at the cell surface due to the inability to selectively visualise channels at the surface. Although N - type channels are thought to consist of a Ca v 2.2, α 2 δ and β subunits, there is uncertainty over whether the pore forming Ca v 2.2 subunit does indeed interact with α 2 δ at the cell surface. The work in this thesis has yielded two tagged ...
A method of manufacturing a flash memory semiconductor device that eliminates the step of forming sidewall spacers on n-channel and p-channel transistor gate structures. Resist spacers having a dimension of Gn+2Sn are formed on n-channel transistor gate structures and an N+ implant is performed to form N+ implant is performed to form N+ regions in the n-channel substrate region. Resist spacers having a dimension of Gs +2Sp are formed on p-channel transistor gate structures and a P+ implant is performed to form P+ regions in the p-channel substrate region.
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Burke, Julian F and Thomas, Sandy (1999) Eli Lilly: DNA patenting through the ages. Expert Opinion on Therapeutic Patents, 9. pp. 119-127. ISSN 1354-3776 Cox, Brian and Denyer, Jane C (1998) N-type calcium channel blockers in pain and stroke. Expert Opinion on Therapeutic Patents, 8 (10). pp. 1237-1250. ISSN 1354-3776 ...
WORKLIST ENTRIES (1): LVDCCALPHA1D View alignment Voltage-dependent L-type calcium channel alpha-1D subunit signature Type of fingerprint: COMPOUND with 5 elements Links: PRINTS; PR00167 CACHANNEL; PR01629 TVDCCALPHA1; PR01630 LVDCCALPHA1 PRINTS; PR01631 NVDCCALPHA1; PR01632 PQVDCCALPHA1; PR01633 RVDCCALPHA1 PRINTS; PR01634 LVDCCALPHA1S; PR01635 LVDCCALPHA1C Creation date 20-DEC-2001 1. WILLIAMS, M.E., BRUST, P.F., FELDMAN, D.H., PATTHI, S., SIMERSON, S., MAROUFI, A., MCCUE, A.F., VELICELBI, G., ELLIS, S.B. AND HARPOLD, M.M. Structure and functional expression of an omega-conotoxin sensitive human N-type calcium channel. SCIENCE 257 389-395 (1992). 2. MORI, Y., FRIEDRICH, T., KIM, MS., MIKAMI, A., NAKAI, J., RUTH, P., BOSSE, E., HOFMANN, F., FLOCKERZI, V., FURUICHI, T., MIKOSHIBA, K., IMOTO, K., TANABE, T. AND NUMA, S. Primary structure and functional expression from complementary DNA of a brain calcium channel. NATURE 350 398-402 (1991). 3. ASHCROFT, F.M. Voltage-gated Ca2+ channels. IN ION ...
WORKLIST ENTRIES (1): LVDCCALPHA1C View alignment Voltage-dependent L-type calcium channel alpha-1C subunit signature Type of fingerprint: COMPOUND with 13 elements Links: PRINTS; PR00167 CACHANNEL; PR01629 TVDCCALPHA1; PR01630 LVDCCALPHA1 PRINTS; PR01631 NVDCCALPHA1; PR01632 PQVDCCALPHA1; PR01633 RVDCCALPHA1 PRINTS; PR01634 LVDCCALPHA1S; PR01636 LVDCCALPHA1D Creation date 20-DEC-2001 1. WILLIAMS, M.E., BRUST, P.F., FELDMAN, D.H., PATTHI, S., SIMERSON, S., MAROUFI, A., MCCUE, A.F., VELICELBI, G., ELLIS, S.B. AND HARPOLD, M.M. Structure and functional expression of an omega-conotoxin sensitive human N-type calcium channel. SCIENCE 257 389-395 (1992). 2. MORI, Y., FRIEDRICH, T., KIM, MS., MIKAMI, A., NAKAI, J., RUTH, P., BOSSE, E., HOFMANN, F., FLOCKERZI, V., FURUICHI, T., MIKOSHIBA, K., IMOTO, K., TANABE, T. AND NUMA, S. Primary structure and functional expression from complementary DNA of a brain calcium channel. NATURE 350 398-402 (1991). 3. ASHCROFT, F.M. Voltage-gated Ca2+ channels. IN ION ...
SuperFET® III MOSFET is ON Semiconductors brand-new high voltage super-junction (SJ) MOSFET family that is utilizing charge balance technology for
APM3007NU N-Channel Enhancement Mode MOSFET Features • Pin Description 30V/50A, RDS(ON)=5.5mΩ (typ.) @ VGS=10V RDS(ON)=8.5mΩ (typ.) @ VGS=4.5V • • • G Super High Dense Cell Design D S Reliable and Rugged Top View of TO-252 Lead Free Available (RoHS Compliant) D Applications • Power Management in Desktop Computer or G DC/DC Converters S N-Channel MOSFET Ordering and Marking Information Package Code U : TO-252 Operating Junction Temp. Range C : -55 to 150 ° C Handling Code TU : Tube TR : Tape & Reel Lead Free Code L : Lead Free Device Blank : Original Device APM3007N Lead Free Code Handling Code Temp. Range Package Code APM3007N U : APM3007N XXXXX XXXXX - Date Code Note: ANPEC lead-free products contain molding compounds and 100% matte tin plate termination finish; which are fully compliant with RoHS and compatible with both SnPb and lead-free soldiering operations. ANPEC lead-free products meet or exceed the lead-free requirements of IPC/JEDEC J STD-020C for MSL classification at ...
The FDMS7658AS has been designed to minimize losses in power conversion application. Advancements in both silicon and package technologies have been combined
New genetic data have allowed a more precise definition of 1.2.3.1 Familial hemiplegic migraine (FHM) than was possible previously. Specific genetic subtypes have been identified: in FHM1 there are mutations in the CACNA1A gene (coding for a calcium channel) on chromosome 19; in FHM2 there are mutations in the ATP1A2 gene (coding for a K/Na-ATPase) on chromosome 1; and in FHM3 there are mutations in the SCN1A gene (coding for a sodium channel) on chromosome 2. There may be other loci not yet identified. If genetic testing is done, the genetic subtype (if discovered) should be specified at the fifth digit.. It has been shown that 1.2.3.1 Familial hemiplegic migraine (FHM) very often presents with brainstem symptoms in addition to the typical aura symptoms, and that headache almost always occurs. Rarely, during FHM attacks, disturbances of consciousness (sometimes including coma), confusion, fever and CSF pleocytosis can occur.. 1.2.3.1 Familial hemiplegic migraine (FHM) may be mistaken for ...
Objectives Clinical studies have indicated the beneficial effect of an L/N-type calcium channel blocker (CCB) cilnidipine around the progression of proteinuria in hypertensive patients compared with an L-type CCB amlodipine. in an age-dependent manner. Cilnidipine suppressed the proteinuria greater than amlodipine did. The immunohistochemical analysis showed that N-type calcium channel and Wilms tumor factor a marker of podocyte were co-expressed. SHR/ND had significantly greater desmin staining an indication of podocyte injury with lower podocin and nephrin expression in the glomeruli than Wistar-Kyoto rat or SHR. Cilnidipine significantly prevented the increase in desmin staining and restored the glomerular podocin and nephrin expression compared with amlodipine. Cilnidipine also prevented the increase in renal angiotensin II content the expression and membrane translocation of NADPH oxidase subunits and dihydroethidium staining in SHR/ND. In contrast amlodipine failed MUC12 to switch these ...
Highly selective N-type voltage-gated calcium (CaV) channel inhibitors from cone snail venom (the ω-conotoxins) have emerged as a new class of therapeutics for the treatment of chronic and neuropathic pain. Earlier in 2005, Prialt (Elan) or synthetic ω-conotoxin MVIIA, was the first ω-conotoxin to be approved by Food and Drug Administration for human use. This review compares the action of three ω-conotoxins, GVIA, MVIIA and CVID, describing their structure-activity relationships and potential as leads for the design of improved N-type therapeutics that are more useful in the treatment of chronic pain.
The use of organotypic hippocampal-slice cultures to investigate neuronal damage after ischemia or hypoxia presents an ideal model for the study of direct neuronal protective effects of calcium channel antagonists. The cultures retain many of the organizational features of the in vivo hippocampus without a functional vascular component, and thus only neuronal effects of the drugs are observed. Using this model, we have demonstrated a clear concentration-dependent reduction in hypoxia-induced neuronal death by CTX MVIIA. At a concentration of 300 nmol/L, CTX MVIIC was equipotent compared with CTX MVIIA. Neither nifedipine nor SB201823-A was neuroprotective. Neuronal damage induced by ischemia was not prevented by any of the compounds.. It has previously been demonstrated in vivo that CTX MVIIA, but not CTX MVIIC, has potent neuroprotective actions, even when administered many hours after an ischemic episode.11 23 In vitro, delaying the addition of CTX MVIIA until immediately after the hypoxic ...
Voltage-dependent N-type calcium channel subunit alpha-1B (Brain calcium channel III) (BIII) (Calcium channel; L type; alpha-1 polypeptide isoform 5) (Voltage-gated calcium channel subunit alpha Cav2.2 ...
RGK regulation of voltage-gated calcium channels. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
ID A0A151MF56_ALLMI Unreviewed; 2363 AA. AC A0A151MF56; DT 08-JUN-2016, integrated into UniProtKB/TrEMBL. DT 08-JUN-2016, sequence version 1. DT 25-OCT-2017, entry version 11. DE RecName: Full=Voltage-dependent N-type calcium channel subunit alpha {ECO:0000256,RuleBase:RU003808}; GN ORFNames=Y1Q_0005596 {ECO:0000313,EMBL:KYO23157.1}; OS Alligator mississippiensis (American alligator). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Archelosauria; Archosauria; Crocodylia; Alligatoridae; Alligatorinae; OC Alligator. OX NCBI_TaxID=8496 {ECO:0000313,EMBL:KYO23157.1}; RN [1] {ECO:0000313,EMBL:KYO23157.1, ECO:0000313,Proteomes:UP000050525} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=KSC_2009_1 {ECO:0000313,EMBL:KYO23157.1}; RX PubMed=22293439; DOI=10.1186/gb-2012-13-1-415; RA St John J.A., Braun E.L., Isberg S.R., Miles L.G., Chong A.Y., RA Gongora J., Dalzell P., Moran C., Bedhom B., Abzhanov A., RA Burgess S.C., Cooksey A.M., Castoe T.A., Crawford N.G., ...
Animals. The generation and detailed characterization of Cav1.2DHP(-/-) and Cav1.3(-/-) mice has been reported previously (Platzer et al., 2000; Sinnegger-Brauns et al., 2004). Double mutant Cav1.2DHP(-/-) × Cav1.3(-/-) mice were generated by crossing Cav1.3(-/-) male mice with Cav1.2DHP(-/-) female mice previously backcrossed into C57BL/6N background in five generations. Animals heterozygous for both mutant alleles were then crossed to obtain homozygous double mutants (referred to as Cav-DM). Tissues and RNA from 3- to 16-month old male mice or 3- to 12-month old male Sprague-Dawley rats were used for experiments. Animal handling was approved by the Bundesministerium für Bildung, Wissenschaft und Kultur (Vienna, Austria) in accordance with international laws and policies of animal welfare.. Recombinant α1 cDNAs. The following α1 subunit cDNAs were used (GenBank accession numbers given in parentheses): rabbit Cav1.2 (X15539), human Cav1.3 (EU63339; Koschak et al., 2001), and human Cav1.4 ...
We have used all reasonable efforts to ensure that the information displayed on these pages and contained in the databases is of high quality. We make no warranty, express or implied, as to its accuracy or that the information is fit for a particular purpose, and will not be held responsible for any consequences arising out of any inaccuracies or omissions. Individuals, organisations and companies which use this database do so on the understanding that no liability whatsoever either direct or indirect shall rest upon the curator(s) or any of their employees or agents for the effects of any product, process or method that may be produced or adopted by any part, notwithstanding that the formulation of such product, process or method may be based upon information here provided ...
Ulises Meza, Ashish Thapliyal, Roger A Bannister, Brett A Adams. Mol. Pharmacol., 2007 Jan , 71, 284-93. Neurokinin (NK) 1 receptors and CaV2.3 calcium channels are both expressed in nociceptive neurons, and mice lacking either protein display altered responses to noxious stimuli. Here, we examined modulation of CaV2.3 through NK1 receptors expressed in human embryonic kidney 293 cells. We find that NK1 receptors generate complex modulation of CaV2.3. In particular, weak activation of these receptors evokes mainly stimulation of CaV2.3, whereas strong receptor activation elicits profound inhibition that overlaps with channel stimulation. Unlike R-type channels encoded by CaV2.3, L-type (CaV1.3), N-type (CaV2.2), and P/Q-type (CaV2.1) channels are inhibited, but not stimulated, through NK1 receptors. Pharmacological experiments show that protein kinase C (PKC) mediates stimulation of CaV2.3 through NK1 receptors. The signaling mechanisms underlying inhibition were explored by expressing proteins ...
After contact holes for the P- and N-type source or drain regions of P- and N-channel MOSFETs have been made at a common step, an N-type impurity is ion-implanted into at least the N-type source or drain regions through the contact holes. The N-type impurity is annealed to fornm an N-type region which is deeper than the N-type source or drain regions. During the annealing treatment, the N-type source or drain regions are covered with an insulating film.
A CMOS device wherein the N-channel devices have n+ gates, and the P-channel devices have p+ gates. A TiN local interconnect system is used to connect the two types of gates, as well as providing connections to moat.
ST Microelectronics STW55NE10 datasheet, N-CHANNEL MOSFET (1-page), STW55NE10 datasheet, STW55NE10 pdf, STW55NE10 datasheet pdf, STW55NE10 pinouts
Raffaella G., Sole,C., Llecha,N, Segura, M.F., Moubarak,R., Iglesias-Guimarais,V., Perez-Garcia,M.J., Reix,S., Zhang,J., Badiola,N., Sanchis,D., Rodriguez-Alvarez,J.,Trullas,R., Yuste,V.J., and J.X. Comella ...
TY - JOUR. T1 - Familial hemiplegic migraine in a child with seizure disorder. T2 - Clinical history is the key to diagnosis. AU - Balakrishnan, Pranav. AU - Katakam, Phalguna Kousika. AU - Hegde, Asha P.. PY - 2019/3/1. Y1 - 2019/3/1. N2 - Headache is a common presenting complaint in the paediatric population, with often migraine being a clinical diagnosis. Hemiplegic migraine is characterised by aura, sudden onset weakness of one side of the body which usually recovers without any residual neurological deficit. We report a child with a history of seizure disorder, well controlled and off medication for 3 years, who presented with a headache, aura and transient hemiplegia. Similar history in the patients mother suggests the diagnosis of familial hemiplegic migraine. We would like to emphasise the importance of detailed history as an important aid in the diagnosis of neurological disorders in children.. AB - Headache is a common presenting complaint in the paediatric population, with often ...
RecName: Full=Voltage-dependent P/Q-type calcium channel subunit alpha-1A;AltName: Full=Voltage-gated calcium channel subunit alpha Cav2.1;AltName: Full=Calcium channel, L type, alpha-1 polypeptide isoform 4;AltName: Full=Brain calcium channel I; Short=BI ...
Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels (Cav). In vivo, this toxin is a potent paralytic toxic in lower vertebrate species, but it is much less effective in mammals.
The IUPHAR/BPS Guide to Pharmacology. Cav1.3 - Voltage-gated calcium channels. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
Real-time qPCR analysis of all α2δ subunit isoforms indicated that neonatal IHCs express mainly α2δ2, whereas mature IHCs exclusively express α2δ2 mRNA. The low expression of α2δ3 mRNA detected in IHCs before hearing onset is in accordance with a small reduction of the Ba2+ current density in immature IHCs of α2δ3−/− mice (Pirone et al., 2014). α2δ2 mRNA was clearly present in both immature and mature IHCs and OHCs. Its low level at P20-P25 can be explained by the downregulation of Cav1.3 currents during development to only one-third of the level present at P6 in IHCs (Beutner and Moser, 2001; Johnson et al., 2005) and similarly also in OHCs (Knirsch et al., 2007). The fact that α2δ1, α2δ3, and α2δ4 mRNA were not detected indicates that α2δ2 is the dominant α2δ isoform that forms Ca2+ channels with Cav1.3 and Cavβ2 in mature IHCs. Interestingly, this L-type channel complex (CaV1.3/β2/α2δ2) is distinct from the P/Q-type channel complex in cerebellar Purkinje cells, ...
Voltage-dependent calcium channel subunit alpha-2/delta-1 (CA2D1) antibody | P54289 | Voltage-dependent calcium channel subunit alpha-2/delta-1, Voltage-gated calcium channel subunit alpha-2/delta-1, CACNL2A, CCHL2A, MHS3
RecName: Full=Voltage-dependent calcium channel subunit alpha-2/delta-4;AltName: Full=Voltage-gated calcium channel subunit alpha-2/delta-4;Contains: RecName: Full=Voltage-dependent calcium channel subunit alpha-2-4;Contains: RecName: Full=Voltage-depen ...
N-channel, metal-oxide-silicon, field-effect transistors (MOSFETs) often utilize additional P-type (boron) doping under the thick, field, isolation oxid...
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1 Answer (question resolved) - Posted in: cartia xt, high blood pressure - Answer: Cartia XT is an extended release calcium channel beta blocker. I ...
View mouse Cacna1s Chr1:136052805-136119822 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent…
Wang PH, Schwindt TT, Barnabé GF, Motta FL, Semedo P, Beraldo FC, Mazzali M, Dos Reis MA, Teixeira VD, Pacheco-Silva A, Mello LE, Câmara NO ...
Epidemiological studies have shown that sporadic cases occur with approximately the same prevalence as familial cases.. The attacks in 1.2.3.2 Sporadic hemiplegic migraine have the same clinical characteristics as those in 1.2.3.1 Familial hemiplegic migraine. Some apparently sporadic cases have known FHM mutations, and in some a first- or second-degree relative later develops hemiplegic migraine, thus completing fulfilment of the criteria for 1.2.3.1 Familial hemiplegic migraine and requiring a change of diagnosis.. Sporadic cases usually require neuroimaging and other tests to rule out other causes. A lumbar puncture may be necessary to rule out 7.8 Syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL).. ...
Voltage-dependent calcium channels represent a major pathway of calcium entry into neurons, where they participate actively to cell excitability and to the molecular processes of synaptic transmission. For that reason, they have been the direct or indirect pharmacological targets of analgesics and this long before their implication in the physiology of nociception had been demonstrated. These last years, the still more refined molecular characterization of these channels and their associated regulatory subunits and the demonstration of their implication in nociceptive processes indicates that these structures are prime pharmacological targets for the management of pain. Herein, we detail the recent breakthroughs on calcium channel structure, function and pharmacology, review the implication of calcium channels in the transmission of nociception, and evaluate their importance as targets for the treatment of pain perception. The search for specific inhibitors of voltage-dependent calcium channels appears
Supplementary Materialssensors-20-01322-s001. and the worthiness increased Rabbit Polyclonal to IFI44 to 2.1 k, which was ascribed to the poor chemical conductivity [30]. Due to the reduced graphene oxide, the value of the rGO/DSPE was about 310 . This small semicircle appeared within the rGO/DSPE, which shows that the dynamic performance of the electronic transmission was poor. For the LC-rGO/DSPE, the value increased to 700 , which made the electroanalytical probe unable to reach the electrode surface to participate in the reaction. The results were in agreement with the conclusion from the CV. Open in a separate window Number 3 Electrochemical impedance spectroscopy of the DSPE, LC/DSPE, rGO/DSPE and LC-rGO/DSPE in 5 mmol/L [Fe(CN)6]3-/4? and 0.1 mol/L KCl with frequencies from 1 to 105 Hz. The hydrogen development has a serious effect on the electrochemical response. Hence, this property in the electrode surface was analyzed. As demonstrated in Number 4, the backdrop current from the ...
α-Conotoxins that are thought to act as antagonists of nicotinic acetylcholine receptors (nAChRs) containing α3-subunits are efficacious in several preclinical models of chronic pain. Potent interactions of Vc1.1 with other targets have suggested that the pain-relieving actions of α-conotoxins might be mediated by either α9α10 nAChRs or a novel GABA B receptor-mediated inhibition of N-type calcium channels. Here we establish that three α-conotoxins, Vc1.1, AuIB and MII have distinct selectivity profiles for these three potential targets. Their potencies after intramuscular administration were then determined for reversal of allodynia produced by partial nerve ligation in rats. Vc1.1, which potently inhibits α9α10 nAChRs and GABA B/Ca 2+ channels but weakly blocks α3β2 and α3β4 nAChRs, produced potent, long-lasting reversal of allodynia that were prevented by pre-treatment with the GABA B receptor antagonist, SCH50911. α-Conotoxin AuIB, a weak α3β4 nAChR antagonist, inhibited GABA B/Ca 2+
ID F7HMC6_MACMU Unreviewed; 2280 AA. AC F7HMC6; DT 27-JUL-2011, integrated into UniProtKB/TrEMBL. DT 30-NOV-2016, sequence version 2. DT 25-OCT-2017, entry version 42. DE RecName: Full=Voltage-dependent N-type calcium channel subunit alpha {ECO:0000256,RuleBase:RU003808}; GN Name=CACNA1B {ECO:0000313,Ensembl:ENSMMUP00000012043}; 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:ENSMMUP00000012043, ECO:0000313,Proteomes:UP000006718}; RN [1] {ECO:0000313,Ensembl:ENSMMUP00000012043, ECO:0000313,Proteomes:UP000006718} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=17573 {ECO:0000313,Ensembl:ENSMMUP00000012043, 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 ...
voltage-gated calcium channel complex, high voltage-gated calcium channel activity, voltage-gated calcium channel activity, calcium ion transmembrane transport, calcium-mediated signaling, chemical synaptic transmission, neuromuscular junction development, neuron remodeling, regulation of voltage-gated calcium channel activity
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 ...
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Question - My 10 years old son is suffering from hemiplegic migraine. Ask a Doctor about diagnosis, treatment and medication for Migraine, Ask a Neurologist
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Drug information on brand Cilacar (5 mg) 5mg (10 Tablet) (Cilnidipine). It is manufactured by J.B.Chemicals & Pharmaceuticals Ltd.. Find out its price,dose and the nearest pharmacy to buy it.
Can anyone recommend any newsgroups dealing with calcium channel of SR? Thank you in advance for your help. ssultang (in english, sugar ...
Annotation. The Na,K-ATPase is essential for maintaining the transmembrane ion gradients required for normal cell function. Previous studies clearly indicate that a specific Na,K-ATPase inhibitor, ouabain can initiate Src kinase signaling independently of the effects on Na,K-ATPase mediated ion translocation. This Na,K-ATPase-Src signaling has been shown in the kidney and heart, and seems perfectly suited for modulation of vasoconstriction, but has never been studied in smooth muscle cells. Several findings indirectly suggest the importance of Na,K-ATPase-Src complex for vascular remodeling and elevated contraction in resistance arteries in ouabain-induced and other forms of hypertension. Familial hemiplegic migraine type 2 (FHM2), associated with the loss-of-function mutation in the Na,K-ATPase, is characterized by elevated vascular contractility which might depend on Src activation. We have shown that the Na,K-ATPase-dependent Src activation could increase arterial contraction via ...
Alternative splicing of a pair of mutually exclusive exons (exon 37a and 37b) of the P/Q-type Ca2+ channels produces two different splice variants in the EF-hand region, namely Cav2.1[EFa] and Cav2.1[EFb] channels. Using isoform-specific antibodies against Cav2.1[EFa] and Cav2.1[EFb] channels, we show that Cav2.1[EFa] and Cav2.1[EFb] channels are differentially localized in subcellular compartments of hippocampal, cerebellar and cortical neurons. 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. 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. In addition, a yeast-two-hybrid screen was performed to find potential interacting proteins with the EF-hand of the Cav2.1[EFa] channel. The screen reveals ...
Looking for online definition of calcium channel, voltage-dependent, gamma subunit 6 in the Medical Dictionary? calcium channel, voltage-dependent, gamma subunit 6 explanation free. What is calcium channel, voltage-dependent, gamma subunit 6? Meaning of calcium channel, voltage-dependent, gamma subunit 6 medical term. What does calcium channel, voltage-dependent, gamma subunit 6 mean?
Hemiplegia is a condition where one side of the body is weakened or paralysed. Find out more about the different types of Hemiplegic Migraines and more.
Telmisartan amongst ARBs, acts as a partial agonist of PPAR- γ (Peroxisome Proliferator Activated Receptor- Gamma) receptor, helps in improving blood glucose and lipid profile. Cilnidipine improve GLUT-4 receptor, which lead to increase in glucose uptake. Thus, improve insulin sensitivity. Thus, combination of Telmisartan with Cilnidipine improves glucose levels and insulin sensitivity along with decrease in blood pressure. In Renally compromised patients Telmisartan which is mainly excreted through hepatic route can be safely given to hypertensive patients who suffer from nephropathy and there is no need to reduce the dose. N-type Ca2+ channels are present in both afferent and efferent arterioles. Their inhibition by Cilnidipine elicits vasodilation of both arterioles, leading to the reduction in glomerular pressure. This results in decrease in proteinuria. Thus, combination of telmisartan and Cilnidipine is beneficial in the hypertensives with kidney disease ...
Cacna1c (untagged) - Mouse calcium channel, voltage-dependent, L type, alpha 1C subunit (Cacna1c), transcript variant 11, 10 µg.
annotations (the reliablity of the annotated protein expression using immunohistochemically (IH) stained on human tissues, the reliablity of the annotated protein expression in immunofluorescently (IF) stained human cell lines, tissue specificity (the distribution of antibody staining or protein expression in human cell types), cell line specificity (the distribution of RNA abundance in cell lines) and subcellular location (based on immunofluorescent staining of cell lines ...
2013.6 Undergraduate Research in X-Lab recognized as Excellent Theses WANG Yingqi won one of the two BME slots for excellent undergraduate theses here at Tsinghua; also, LIU Jinxin got similar honor from Chinese Agriculture University (NONG-DA). Congratulations to Yingqi and Jinxin!!! 2013.6 Dr. LIU Xiaodong received Janssen Investigator Award This award is to recognize Dr. LIU Xiaodongs research achievement in mechanisms of voltage-gated calcium channels and on-going efforts in molecular physiology of voltage-gated calcium channels in non-excitable cells (such as T-lymphocytes). http://tjcid.med.tsinghua.edu.cn/ ...
HEK293-HuCACNA1C/CACNB2/CACNA2D1 cell line is a hypotriploid human cell line, which has been transfected with a human calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C), a human calcium channel, voltage-dependent, alpha 2/delta subunit 1 (CACNA2D1) and a human calcium channel, voltage-dependent, beta 2 subunit (CACNB2) to allow stably express of the human CACNA1C, CACNB2, and CACNA2D1. It is an example of a cell line transfected using our proprietary CBTGS gene screening and amplificatio
... calcium channel, voltage-dependent, R type, alpha 1E subunit Identifiers Symbol CACNA1E Alt. Symbols CACNL1A6 Entrez 777 HUGO 1392 OMIM
Compare calcium channel, voltage-dependent, L type, alpha 1S subunit ELISA Kits from leading suppliers on Biocompare. View specifications, prices, citations, reviews, and more.
HEK293-HuCACNA1C/NEUROD1/CACNA2D1/KCNJ2 cell line is a hypotriploid human cell line, which has been transfected with a human calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C), a human neuronal differentiation 1 (NEUROD1), a human calcium channel, voltage-dependent, alpha 2/delta subunit 1 (CACNA2D1) and a human potassium inwardly-rectifying channel, subfamily J, member 2 (KCNJ2) to allow stably express of the human CACNA1C, NEUROD1, CACNA2D1 and KCNJ2. It is an example of a cell line tr
Cilacar T (Cilnidipine/Telmisartan) is a combination of 2 medicines which helps control high blood pressure by widening the peripheral blood vessels so as to improve the flow of blood.
Rabbit polyclonal Two pore calcium channel protein 2 antibody validated for WB, IHC and tested in Human. Immunogen corresponding to synthetic peptide
Hi - this thread was started as a coffee break chat - but I think its such a good discussion thread it deserves its own thread..... wildone wrote: One thing the
TY - JOUR. T1 - Light-activated protein inhibition through photoinduced electron transfer of a ruthenium(II)-cobalt(III) bimetallic complex. AU - Holbrook, Robert J.. AU - Weinberg, David J.. AU - Peterson, Mark D.. AU - Weiss, Emily A.. AU - Meade, Thomas J.. PY - 2015/2. Y1 - 2015/2. N2 - We describe a mechanism of light activation that initiates protein inhibitory action of a biologically inert Co(III) Schiff base (Co(III)-sb) complex. Photoinduced electron transfer (PET) occurs from a Ru(II) bipyridal complex to a covalently attached Co(III) complex and is gated by conformational changes that occur in tens of nanoseconds. Reduction of the Co(III)-sb by PET initiates displacement of the inert axial imidazole ligands, promoting coordination to active site histidines of α-thrombin. Upon exposure to 455 nm light, the rate of ligand exchange with 4-methylimidazole, a histidine mimic, increases by approximately 5-fold, as observed by NMR spectroscopy. Similarly, the rate of α-thrombin inhibition ...
Looking for online definition of calcium channel, L type, alpha 2 polypeptide in the Medical Dictionary? calcium channel, L type, alpha 2 polypeptide explanation free. What is calcium channel, L type, alpha 2 polypeptide? Meaning of calcium channel, L type, alpha 2 polypeptide medical term. What does calcium channel, L type, alpha 2 polypeptide mean?
Definition of calcium channel blocking agent in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is calcium channel blocking agent? Meaning of calcium channel blocking agent as a finance term. What does calcium channel blocking agent mean in finance?
0027] The invention provides methods and systems for controlling the rectification of the current. In some embodiments, a lighting device includes a rectifier, for example, operably coupled to the printed circuit board. Rectification is a means for keeping the current that goes to the LEDs at the desired amperage regardless of the source of the power. Through the use of a rectifier, the circuit on the circuit board may be a constant current source, which means that it keeps the LED brightness constant no matter what power supply is used or surrounding environmental conditions one subjects the LEDs to. Rectification of the current may be done by a circuit printed on the circuit board that uses, for example, resistors, small NPN transistors, large N-channel FET or other devices as needed depending upon the overall design of the circuit board. By not using constant current drivers, the expense on drivers for the overall system is significantly decreased. Rectifiers for LED systems are discussed in ...
Gene Information The protein encoded by this gene is the pore-forming subunit of an N-type voltage-dependent calcium channel which controls neurotransmitter release from neurons. The encoded protein forms a complex with alpha-2 beta and delta subunits to form the high-voltage activated channel. This channel is sensitive to omega-conotoxin-GVIA and omega-agatoxin-IIIA but insensitive to dihydropyridines. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq Aug 2011]. ...
annotations (the reliablity of the annotated protein expression using immunohistochemically (IH) stained on human tissues, the reliablity of the annotated protein expression in immunofluorescently (IF) stained human cell lines, tissue specificity (the distribution of antibody staining or protein expression in human cell types), cell line specificity (the distribution of RNA abundance in cell lines) and subcellular location (based on immunofluorescent staining of cell lines ...
Calcium channel L type DHPR alpha 2 subunit兔多克隆抗体(ab42586)可与人样本反应并经WB实验严格验证,被1篇文献引用。所有产品均提供质保服务,中国75%以上现货。
Voltage-gated calcium channels are multi-subunit membrane proteins which transduce depolarization into cellular functions like excitation-contraction coupling in muscle or neurotransmitter release in neurons. The auxiliary β subunits function in membrane targeting of the channel and modulation of its gating properties. However, whether β subunits can reversibly interact with, and thus differentially modulate channels in the membrane is still unresolved. Here we applied fluorescence recovery after photobleaching (FRAP) of GFP-tagged α1 and β subunits expressed in dysgenic myotubes to study the relative dynamics of these calcium channel subunits for the first time in a native functional signaling complex. Identical fluorescence recovery rates of both subunits indicate stable interactions, distinct rates dynamic interactions. Whereas the skeletal muscle β1a isoform formed stable complexes with CaV1.1 and CaV1.2, the non-skeletal muscle β2a and β4b isoforms dynamically interacted with both ...
Calcium channel blockers are drugs that block the entry of calcium into the cells of the heart and blood vessels walls by interacting with calcium channels. They are primarily used to treat hypertension, angina and arrhythmias. Learn about the different classes of calcium channel blocker medications and how they are used.
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 ...
A CMIS transistor suitable for device miniaturization, elimination of degradation of operational characteristics by hot carrier effect, and elimination of decrease of threshold voltage caused by short channel effect, includes a laterally spreading N-type diffusion region having an impurity concentration level higher than P-type and N-type wells but lower than source and drain regions, such that the N-type diffusion region extends laterally into a part located immediately below an edge of an insulating gate and has a depth smaller than a depth of the source and drain regions. The device is thereby capable of increasing the width of depletion layer at the bottom of the source and drain regions while maintaining effectiveness as a punch-thorough stopper. Thereby, the junction capacitance at the source and drain regions is reduced and the operational speed of the device improved in the P-channel transistor part in the device. In the N-channel transistor part, an effective suppression of punch-through is
Frequency of genetic polymorphism of calcium channels gene CACNA1C in healthy individuals and patients with arterial hypertension
SO-67 is not scheduled for user access this weekend......... George, KA3HSW ----- Original Message ----- From: Louis House ,kd5gm at sbcglobal.net, To: ,amsat-bb at amsat.org, Sent: Saturday, December 12, 2009 8:14 PM Subject: [amsat-bb] SO-67 ORBIT 1313 To all interested. I tracked the SO-67 orbit 1313 (12-13-09, 0147Z) from EL29kq to a max el. of 9 degrees. I made several calls and had s2 to s4 signals coming back (via SP432VGD assistance) but no audio. I did hear very short pings at regular intervals that registered s6. Louis KD5GM ...
The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
CACNA2D2 - CACNA2D2 (Myc-DDK-tagged)-Human calcium channel, voltage-dependent, alpha 2/delta subunit 2 (CACNA2D2), transcript variant 3 available for purchase from OriGene - Your Gene Company.
總周邊血管阻力(Total Peripheral Resistance,TPR)可由下列數學公式表示:. R = ΔP/Q[2]. R 代表 TPR。 ΔP 代表全身體循環起終點的血壓變化量。 Q 代表心輸出量. 因此此公式可以解釋為. 總周邊血管阻力 = (平均動脈壓 - 平均靜脈壓)/ 心輸出量. 因此平均動脈壓可以下列公式定義:[3]. ...
Homo sapiens calcium channel, voltage-dependent, alpha 1G subunit (CACNA1G), transcript variant 13, mRNA. (H00008913-R13) - Products - Abnova
Homo sapiens calcium channel, voltage-dependent, alpha 1G subunit (CACNA1G), transcript variant 6, mRNA. (H00008913-R08) - Products - Abnova
TY - JOUR. T1 - Restoration of motor defects caused by loss of drosophila TDP-43 by expression of the voltage-gated calcium channel, cacophony, in central neurons. AU - Lembke, Kayly M.. AU - Scudder, Charles. AU - Morton, David. PY - 2017/9/27. Y1 - 2017/9/27. N2 - Defects in the RNA-binding protein, TDP-43, are known to cause a variety of neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal lobar dementia. A variety of experimental systems have shown that neurons are sensitive to TDP-43 expression levels, yet the specific functional defects resulting from TDP-43 dysregulation have not been well described. Using the Drosophila TDP-43 ortholog TBPH, we previously showed that TBPH-null animals display locomotion defects as third instar larvae. Furthermore, loss of TBPH caused a reduction in cacophony, a Type II voltage-gated calcium channel, expression and that genetically restoring cacophony in motor neurons in TBPH mutant animals was sufficient to rescue the ...
A display and a driving method for the same capable of constructing clear visual images as described. In the display, a plurality of conductive pads are opposed to a back electrode with a light influencing medium such as a liquid crystal layer. Control signals are supplied to the conductive pads through complimentary transistors comprise a p-channel field effect transistor and an n-channel field effect transistor connected between V DD and V SS lines of a control circuit, which also supplies a bias voltage to the back electrode and gate control signals to the gate terminals of the p-channel field effect transistor and the n-channel field effect transistor. During operation, the bias voltage is inverted in order to invert the polarity of control signal applied across the light influencing medium.
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 ...
My research focuses on the involvement of two voltage-gated calcium channel mutations in epilepsy. Epilepsy is a neurological disorder characterized by spontaneous seizures that can cause brain damage. In epilepsy, the normal pattern of neuronal activity becomes disturbed, causing convulsions, muscle spasms, and the loss of consciousness. Epilepsy may develop because of an abnormality in brain wiring, an imbalance in neurotransmitters, changes in ion channels, or some combination of these factors.. Ion channels are cell membrane proteins that allow the passage of ions, such as calcium, into or out of the cell, which generates the electrical signals of neural networks. Voltage-gated calcium channels are a type of ion channel, which allows the passage of calcium ions into the cell. They have a pore through which calcium passes, and one or more auxiliary subunits that regulate pore opening and closing. The auxiliary subunit my research focuses on is the β subunit. The β subunit functions in ...
... is classified as a selective antagonist of T-type voltage-operated calcium ion channels, because its binding blocks ... Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group.[1] It is also known to ... Arab SF, Düwel P, Jüngling E, Westhofen M, Lückhoff A (June 2004). "Inhibition of voltage-gated calcium currents in type II ... hypothesized that cinnarizine exerts its effects by inhibiting the calcium currents in voltage gated channels in type II ...
"Osteoprotegerin expression and secretion are regulated by calcium influx through the L-type voltage-sensitive calcium channel ... This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ... Calcium channel, voltage-dependent, L type, alpha 1C subunit (also known as Cav1.2) is a protein that in humans is encoded by ... Berger SM, Bartsch D (Aug 2014). "The role of L-type voltage-gated calcium channels Cav1.2 and Cav1.3 in normal and ...
"Molecular characterization of T-type calcium channels". Cell Calcium. 40 (2): 89-96. doi:10.1016/j.ceca.2006.04.012. PMID ... Seizures are believed to originate in the thalamus, where there is an abundance of T-type calcium channels such as those ... a T-type calcium channel". J Neurosci. 25 (19): 4844-55. doi:10.1523/JNEUROSCI.0847-05.2005. PMID 15888660. Liang J, Zhang Y, ... "Gating effects of mutations in the Cav3.2 T-type calcium channel associated with childhood absence epilepsy". J Biol Chem. 279 ...
Voltage-dependent calcium channel gamma-3 subunit is a protein that in humans is encoded by the CACNG3 gene. L-type calcium ... This gene is a member of the neuronal calcium channel gamma subunit gene subfamily of the PMP-22/EMP/MP20 family. This gene is ... "Entrez Gene: CACNG3 calcium channel, voltage-dependent, gamma subunit 3". Powers PA, Liu S, Hogan K, Gregg RG (1993). " ... It is an integral membrane protein that is thought to stabilize the calcium channel in an inactive (closed) state. This protein ...
Voltage-dependent calcium channel gamma-1 subunit is a protein that in humans is encoded by the CACNG1 gene. L-type calcium ... 1993). "Localization of the gamma-subunit of the skeletal muscle L-type voltage-dependent calcium channel gene (CACNLG) to ... and gamma-subunits of the human skeletal muscle L-type voltage-dependent calcium channel on chromosome 17q and exclusion as ... This gene is a member of the neuronal calcium channel gamma subunit gene subfamily of the PMP-22/EMP/MP20 family and is located ...
Voltage-dependent calcium channel gamma-4 subunit is a protein that in humans is encoded by the CACNG4 gene. L-type calcium ... This gene is a member of the neuronal calcium channel gamma subunit gene subfamily of the PMP-22/EMP/MP20 family and is located ... "Entrez Gene: CACNG4 calcium channel, voltage-dependent, gamma subunit 4". Gerhard DS, Wagner L, Feingold EA, et al. (2004). " ... Voltage-dependent calcium channel GRCh38: Ensembl release 89: ENSG00000075461 - Ensembl, May 2017 GRCm38: Ensembl release 89: ...
L-type calcium channels are composed of five subunits. The protein encoded by this gene represents one of these subunits, gamma ... Calcium channel, voltage-dependent, gamma subunit 2, also known as CACNG2 or stargazin is a protein that in humans is encoded ... This gene is a member of the neuronal calcium channel gamma subunit gene subfamily of the PMP-22/EMP/MP20 family. Stargazin is ... It is an integral membrane protein that is thought to stabilize the calcium channel in an inactive (closed) state. This protein ...
1998). "An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness". Nat. Genet. 19 (3 ... a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell ... Cav1.4 also known as the calcium channel, voltage-dependent, L type, alpha 1F subunit (CACNA1F), is a human gene. This gene ... CACNA1F calcium channel, voltage-dependent, L type, alpha 1F subunit". Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J ( ...
Proximal muscle weakness is a product of pathogenic autoantibodies directed against P/Q-type voltage-gated calcium channels, ... which activates voltage-dependent calcium channels to allow calcium ions to enter the neuron. Calcium ions bind to sensor ... This type of tumor also expresses voltage-gated calcium channels. Oftentimes, LEMS also occurs alongside myasthenia gravis. ... Upon the arrival of an action potential at the presynaptic neuron terminal, voltage-dependent calcium channels open and Ca2+ ...
The T-type calcium channel is found in neurons throughout the brain. These channels produce particularly large currents in ... Recent research has also been conducted on the T-type calcium channel and how modulation of these channels may allow for the ... Antiepileptic drugs can control absence seizures by inhibiting the T-type calcium channels which prevents low-voltage calcium ... T-type calcium channels have been known to play a role in the spike-and-wave discharges of absence seizures. ...
Sodium channel, voltage-gated, type XI, alpha subunit also known as SCN11A or Nav1.9 is a voltage-gated sodium ion channel ... Nomenclature and structure-function relationships of voltage-gated calcium channels". Pharmacological Reviews. 57 (4): 411-25. ... "Entrez Gene: Sodium channel, voltage-gated, type XI, alpha subunit". Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J ( ... This property is found in similar channels, namely Nav1.8, and has been associated with slower channel kinetics than the ...
Structural model for phenylalkylamine binding to L-type calcium channels. The Journal of Biological Chemistry, 284(41), 28332- ... The drug targets L-type Ca+2 channels, and decreases conduction in cells where Ca+2 is required for action potential upstroke ( ... 1995). Electrophysiological effect of BRL-32872, a novel antiarrhythmic agent with potassium and calcium channel blocking ... BRL-32872's class III activity is directed towards the human ether-a-go-go-related gene (hERG) K+ channel. hERG channels are ...
The voltage-dependent N-type calcium channel subunit alpha-1B is a protein that in humans is encoded by the CACNA1B gene. ... subunits for the calcium channel I-II linker in relation to calcium channel function". The Journal of Physiology. 574 (Pt 2): ... Maximov A, Bezprozvanny I (Aug 2002). "Synaptic targeting of N-type calcium channels in hippocampal neurons". The Journal of ... Calabrese B, Tabarean IV, Juranka P, Morris CE (Nov 2002). "Mechanosensitivity of N-type calcium channel currents". Biophysical ...
... (INN) is a calcium channel blocker. It is a calcium antagonist accompanied with L-type and N-type calcium channel ... Unlike other calcium antagonists, cilnidipine can act on the N-type calcium channel in addition to acting on the L-type calcium ... Due to its blocking action at the N-type and L-type calcium channel, cilnidipine dilates both arterioles and venules, reducing ... May 2002). "Cilnidipine is a novel slow-acting blocker of vascular L-type calcium channels that does not target protein kinase ...
N-type calcium-channel blocker.. Intrathecal.. Protein binding = 50%; half-life = 2.9-6.5 hours; excretion = urine (,1%).[122] ... Binds to the α2δ-1 subunit of voltage gated calcium ion channels in the spinal cord. May also modulate NMDA receptors and ... Comes in calcium salt form; fairly soluble in water.. Is metabolised to aspirin and urea. As per aspirin.. Oral.. No data.. ... Each different type of analgesic has its own associated side effects. Classification[edit]. Analgesics are typically classified ...
... type-1) and atypical (type-2). They are both caused by mutations in CACNA1C, the gene encoding the calcium channel Cav1.2 α ... "Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations". Proc Natl Acad Sci USA. 102 (23): 8089-8096. ... Cav1.2 Calcium channel Marks M, Whisler S, Clericuzio C, Keating M (1995). "A new form of long QT syndrome associated with ... However, it was linked with calcium channel abnormalities in 2004, and the disorder was thence named "Timothy syndrome" in ...
... calcium channel blocker, inhibits both L-type and T-type calcium channels. Efonidipine exhibits antihypertensive effect through ... It was launched in 1995, under the brand name Landel (ランデル). The drug blocks both T-type and L-type calcium channels. Drug ... Efonidipine is a dual Calcium Channel Blocker (L & T-type). It has a unique chemical structure. The phosphonate moiety (Figure ... Working on sino atrial node cells by inhibiting T-type calcium channel activation, Efonidipine prolongs the late phase-4 ...
Calcium Channels (L-Type). It is the first positive inotropic agent shown to act specifically and directly on calcium channels ... Bay K8644 is a chemical compound that functions as a calcium channel agonist. Bay K8644 is used primarily as a biochemical ... that enhances calcium currents in guinea pig and calf myocardial cells. A new type of positive inotropic agent". Circ Res. 56: ...
"Modulation of A-type potassium channels by a family of calcium sensors". Nature. 403 (6769): 553-556. doi:10.1038/35000592. ... They are integral subunit components of native Kv4 channel complexes. They may regulate A-type currents, and hence neuronal ... "Entrez Gene: KCNIP1 Kv channel interacting protein 1". Burgoyne RD (2007). "Neuronal calcium sensor proteins: generating ... 2001). "Conserved Kv4 N-terminal domain critical for effects of Kv channel-interacting protein 2.2 on channel expression and ...
... on recombinant T-type channels in cell lines demonstrated conclusively that ethosuximide blocks all T-type calcium channel ... and α1I T-type calcium channels, Gomora's team found that ethosuximide blocked the channels with an IC50 of 12 ± 2 mmol/L and ... Gomora JC, Daud AN, Weiergraber M, Perez-Reyes E (2001). "Block of cloned human T-type calcium channels by succinimide ... The primary finding that ethosuximide is a T-type calcium channel blocker gained widespread support, but initial attempts to ...
The relative permeability of calcium and magnesium varies widely among TRPM channels. TRPM4 and TRPM5 are impermeable to ... TRPM6 and TRPM7, for example, contain functional α-kinase segments, which are a type of serine/threonine-specific protein ... Among the functional responsibilities of the TRPM channels are: regulation of calcium oscillations after T cell activation and ... TRPM is a family of transient receptor potential ion channels (M standing for melastatin). Functional TRPM channels are ...
"Modulation of A-type potassium channels by a family of calcium sensors". Nature. 403 (6769): 553-6. doi:10.1038/35000592. PMID ... They are integral subunit components of native Kv4 channel complexes. They may regulate A-type currents, and hence neuronal ... "Entrez Gene: KCNIP2 Kv channel interacting protein 2". Burgoyne RD (Mar 2007). "Neuronal calcium sensor proteins: generating ... Ren X, Shand SH, Takimoto K (Oct 2003). "Effective association of Kv channel-interacting proteins with Kv4 channel is mediated ...
"Modulation of A-type potassium channels by a family of calcium sensors". Nature. 403 (6769): 553-6. doi:10.1038/35000592. PMID ... Schrader LA, Anderson AE, Mayne A, Pfaffinger PJ, Sweatt JD (2002). "PKA modulation of Kv4.2-encoded A-type potassium channels ... They are integral subunit components of native Kv4 channel complexes that may regulate A-type currents, and hence neuronal ... "Entrez Gene: KCNIP3 Kv channel interacting protein 3, calsenilin". Burgoyne RD (2007). "Neuronal Calcium Sensor Proteins: ...
... are also involved in regulation of channels and in calcium signaling. Caveolae also participate in lipid regulation. ... This type of endocytosis is used for example for transcytosis of albumin in endothelial cells or for internalization of the ... Caveolae have been shown to be required for the protection of cells from mechanical stress in multiple tissue types such as the ... In biology, caveolae (Latin for "little caves"; singular, caveola), which are a special type of lipid raft, are small (50-100 ...
This depolarizes the β cells and causes voltage-gated calcium channels to open. The resulting calcium influx induces fusion of ... are affected with type 1 (namely insulin-dependent) diabetes mellitus. are in diabetic ketoacidosis. A study funded by Novo ... Nateglinide (INN, trade name Starlix) is a drug for the treatment of type 2 diabetes. Nateglinide was developed by Ajinomoto, a ... It achieves this by closing ATP-dependent potassium channels in the membrane of the β cells. ...
Models of this type are typically built in large simulation platforms like GENESIS or NEURON. There have been some attempts to ... With the emergence of two-photon microscopy and calcium imaging, we now have powerful experimental methods with which to test ... Voltage sensitive ion channels are glycoprotein molecules which extend through the lipid bilayer, allowing ions to traverse ... "Intracellular Calcium Dynamics Permit a Purkinje Neuron Model to Perform Toggle and Gain Computations Upon its Inputs" ...
The R-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α1 subunit forms ... "Entrez Gene: CACNA1E calcium channel, voltage-dependent, R type, alpha 1E subunit". Soong TW, Stea A, Hodson CD, Dubel SJ, ... This α1 subunit is also known as the calcium channel, voltage-dependent, R type, alpha 1E subunit (CACNA1E) or Cav2.3 which in ... They are poorly understood, but like Q-type calcium channels, they appear to be present in cerebellar granule cells. They have ...
Second, if calcium entry through N-type calcium channels is prevented, the delayed generation of damage is prevented. ... Background and Purpose Neuroprotection by antagonists of both L-type and N-type calcium channels occurs in in vivo models of ... that neuroprotection by selective N-type calcium channel antagonists is mediated directly through neuronal calcium channels. In ... and Q-type channels in addition to blocking N-type channels. Valentino et al11 confirmed in vivo that CTX MVIIC was a much more ...
... expresses T-type calcium current was employed to show that inhibiting calcium influx through the T-type calcium channel ... L-type, and a low voltage activated (LVA) T-type. Influx of calcium into the cell through the L-type channel is responsible for ... Furthermore, blocking the calcium influx through the T-type calcium channel arrests cells in the G2/M phase of the cell cycle. ... Calcium Influx via the T-Type Calcium Channel Plays a Permissive Role in Proliferation of Mouse Embryonic Hl-1 Cells. Welcome ...
... piperazine derivatives as T-type calcium channel blockers",. abstract = "To obtain selective and potent inhibitor for T-type ... N2 - To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 2-hydroxy-3-phenoxypropyl ... AB - To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 2-hydroxy-3-phenoxypropyl ... To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 2-hydroxy-3-phenoxypropyl ...
T-type calcium channels in burst-firing, network synchrony, and epilepsy.. Cain SM1, Snutch TP. ... In this review we summarize recent findings concerning the role of T-type calcium channels in burst-firing and discuss how they ... Low voltage-activated (LVA) T-type calcium channels are well regarded as a key mechanism underlying the generation of neuronal ... Publication types, MeSH terms, Substances, Grant support. Publication types. *Research Support, Non-U.S. Govt ...
Among the many types of voltage-gated Ca2+ channel, L-type Ca2+ channels particularly display inactivation and facilitation, ... Calmodulin supports both inactivation and facilitation of L-type calcium channels.. Zühlke RD1, Pitt GS, Deisseroth K, Tsien RW ... L-type Ca2+ channels support Ca2+ entry into cells, which triggers cardiac contraction, controls hormone secretion from ... Publication types, MeSH terms, Substances. Publication types. *Research Support, Non-U.S. Govt ...
Calcium channel blockers are drugs used to lower blood pressure. Learn more from WebMD about how they work and their side ... certain drugs may interact with calcium channel blockers.. How Should I Take Calcium Channel Blockers?. Most calcium channel ... Interactions With Calcium Channel Blockers Calcium channel blockers are drugs used to lower blood pressure. They work by ... Side Effects of Calcium Channel Blockers. Potential side effects from taking a calcium channel blocker include:. * Dizziness or ...
... which inhibits the T-type calcium channel Cav3.2. This calcium channel was highly expressed in human GBM specimens and enriched ... Targetable T-type Calcium Channels Drive Glioblastoma. Ying Zhang, Nichola Cruickshanks, Fang Yuan, Baomin Wang, Mary Pahuski, ... Targetable T-type Calcium Channels Drive Glioblastoma. Ying Zhang, Nichola Cruickshanks, Fang Yuan, Baomin Wang, Mary Pahuski, ... Targetable T-type Calcium Channels Drive Glioblastoma. Ying Zhang, Nichola Cruickshanks, Fang Yuan, Baomin Wang, Mary Pahuski, ...
... were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or Cav2.2 channel ... Keywords: N-type calcium channel; Cav2.2; channel blocker; pain; FLIPR N-type calcium channel; Cav2.2; channel blocker; pain; ... were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or Cav2.2 channel ... Inhibition of N-Type Calcium Channels by Fluorophenoxyanilide Derivatives. Ellen C. Gleeson 1,2. ...
Mus musculus calcium channel, voltage-dependent, T type, alpha 1G subunit (Cacna... Mus musculus calcium channel, voltage- ... Mus musculus calcium channel, voltage-dependent, T type, alpha 1G subunit (Cacna1g), transcript variant 3, mRNA. NCBI Reference ... See the reference protein sequence for voltage-dependent T-type calcium channel subunit alpha-1G isoform c (NP_001171359.1). ... Calcium Regulation in the Cardiac Cell Calcium Regulation in the Cardiac CellCalcium is a common signaling mechanism, as once ...
Voltage-dependent calcium channel, L-type, alpha-1 subunit (IPR005446) *Voltage-dependent calcium channel, L-type, alpha-1S ... while the Cav3 family mediates T-type calcium currents.. L-type calcium channels are formed from alpha-1S, alpha-1C, alpha-1D, ... The Cav1 family forms channels mediating L-type calcium currents, the Cav2 family mediates P/Q-, N-, and R-type calcium ... Nomenclature of voltage-gated calcium channels.. Neuron 25 533-5 2000. Triggle DJ. 1,4-Dihydropyridines as calcium channel ...
R type, alpha 1E subunit Identifiers Symbol CACNA1E Alt. Symbols CACNL1A6 Entrez 777 HUGO 1392 OMIM ... R-type calcium channel calcium channel, voltage-dependent, ... Calcium channel. Voltage-dependent calcium channel (L-type/Cavα ... The R-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α1 subunit is the ... 1.1, 1.2, 1.3, 1.4), N-type, P-type/Cavα(2.1), Q-type, R-type, T-type, β-subunits (β1, β2, β4), γ-subunits (γ2) • Inositol ...
2011) Location of release sites and calcium-activated chloride channels relative to calcium channels at the photoreceptor ... Lateral Mobility of Presynaptic L-Type Calcium Channels at Photoreceptor Ribbon Synapses. Aaron J. Mercer, Minghui Chen and ... 2004) Role of lipid microdomains in P/Q-type calcium channel (Cav2.1) clustering and function in presynaptic membranes. J Biol ... 2004) The CACNA1F gene encodes an L-type calcium channel with unique biophysical properties and tissue distribution. J Neurosci ...
Long-Lasting calcium channels). The new T-type channels were much different from the L-type calcium channels due to their ... T-type calcium channels are low-voltage activated calcium channels that open during membrane depolarization. These channels aid ... Calcium channel blockers (CCB) such as mibefradil can also block L-type calcium channels, other enzymes, as well as other ... Novel T-type calcium channel inhibitors have recently been discovered which more selectively target the CaV3.3 channel sub-type ...
... which is also similar to another type of calcium channels, known as P-type calcium channels. N-type calcium channels are ... N-type calcium channels are voltage gated calcium channels that are distributed throughout the entire body. These channels are ... The inhibition of this channel by calcium channel blockers can lead to renal microcirculation. N-type calcium channels have ... N-type calcium channels have known functions in the kidney, and heart. There are many known N-type calcium channel blockers, ...
The L-type calcium channel (also known as the dihydropyridine channel, or DHP channel) is part of the high-voltage activated ... This channel has four subunits (Cav1.1, Cav1.2, Cav1.3, Cav1.4). L-type calcium channels are responsible for the excitation- ... In cardiac myocytes, the L-type calcium channel passes inward Ca2+ current and triggers calcium release from the sarcoplasmic ... Rossier, Michel F. (2016). "T-Type Calcium Channel: A Privileged Gate for Calcium Entry and Control of Adrenal Steroidogenesis ...
The Q-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α1 subunit is the ... They are poorly understood, but like R-type calcium channels, they appear to be present in cerebellar granule cells. They have ... Q-Type Calcium Channel at the US National Library of Medicine Medical Subject Headings (MeSH). ... one that determines most of the channels properties. ...
The P-type calcium channel is a type of voltage-dependent calcium channel. Similar to many other high-voltage-gated calcium ... P-type calcium channels play a similar role to the N-type calcium channel in neurotransmitter release at the presynaptic ... There are many different types of calcium channels, so to prove that the P/Q type calcium channels are directly involved, a P/Q ... corresponds to what is functionally defined as the P-type and Q-type isoforms. P-type and Q-type calcium channels are closely ...
... and 7.5-pS single-channel conductance, we conclude that this channel is a low-voltage-activated T-type calcium channel. ... Molecular characterization of a neuronal low-voltage-activated T-type calcium channel.. Perez-Reyes E1, Cribbs LL, Daud A, ... The molecular diversity of voltage-activated calcium channels was established by studies showing that channels could be ... T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and ...
Tyrosine-kinase-dependent recruitment of RGS12 to the N-type calcium channel.. Schiff ML1, Siderovski DP, Jordan JD, Brothers G ... Gamma-aminobutyric acid (GABA)B receptors couple to Go to inhibit N-type calcium channels in embryonic chick dorsal root ... Publication types, MeSH terms, Substances, Secondary source ID. Publication types. *Research Support, Non-U.S. Govt ... here we show an endogenous agonist-induced tyrosine-kinase-dependent complex of RGS12 and the calcium channel. These results ...
Neurons express multiple types of voltage-gated calcium (Ca2+) channels. Two subtypes of neuronal L-type Ca2+ channels are ... Ca1.2 and CaV1.3 neuronal L-type calcium channels: differential targeting and signaling to pCREB.. Zhang H1, Fu Y, Altier C, ... CaV1.2 and CaV1.3 neuronal L-type calcium channels: differential targeting and signaling to pCREB ... CaV1.2 and CaV1.3 neuronal L-type calcium channels: differential targeting and signaling to pCREB ...
Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage.. Choi DW. ...
... and R-type Ca2+ channels are replaced by P/Q-type Ca2+ channels with development. In contrast, multiple types of Ca2+ channels ... 1991) N-type and L-type calcium channels are present in nerve growth cones. Numbers increase on synaptogenesis. Dev Brain Res ... Using type-specific Ca2+ channel blocker toxins, we have demonstrated that the contributions of N-type Ca2+ channels to ... Among them, the ω-conotoxin GVIA-sensitive N-type channels and the ω-Aga-IVA-sensitive P/Q-type channels mediate fast synaptic ...
2007a) Reducing agents sensitize C-type nociceptors by relieving high-affinity zinc inhibition of T-type calcium channels. J ... 2005) Silencing of the CaV3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception. EMBO J ... Molecular Mechanisms of Lipoic Acid Modulation of T-Type Calcium Channels in Pain Pathway. Woo Yong Lee, Peihan Orestes, ... 2001b) Cav3.2 channel is a molecular substrate for inhibition of T-type calcium currents in rat sensory neurons by nitrous ...
omega-Conotoxin block of N-type calcium channels in frog and rat sympathetic neurons. LM Boland, JA Morrill and BP Bean ... omega-Conotoxin block of N-type calcium channels in frog and rat sympathetic neurons ... omega-Conotoxin block of N-type calcium channels in frog and rat sympathetic neurons ... omega-Conotoxin block of N-type calcium channels in frog and rat sympathetic neurons ...
  • 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. (elsevier.com)
  • Compound 6m and 6q showed high selectivity over hERG channel (IC 50 ratio of hERG/α 1G 6m = 8.5, 6q = 18.38) and they were subjected to measure pharmacokinetics profiles. (elsevier.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)
  • 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)
  • 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)
  • Furthermore, if addition of conotoxin MVIIA was delayed until after the hypoxic episode, a dose-dependent neuroprotective effect was observed, with an IC 50 of 50 nmol/L. In contrast to hypoxia, none of the compounds was neuroprotective in the model of oxygen-glucose deprivation, although it was determined that extracellular calcium was essential for the generation of ischemic damage. (ahajournals.org)
  • Adler AI, Stratton IM, Neil HA, Yudkin JS, Matthews DR, Cull CA, Wright AD, Turner RC, Holman RR (2000) Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. (springer.com)
  • Colliver TL, Hess EJ, Pothos EN, Sulzer D, Ewing AG (2000) Quantitative and statistical analysis of the shape of amperometric spikes recorded from two populations of cells. (springer.com)
  • The action potential will propagate through the sarcolemma to the interior of the muscle fibers eventually leading to an increase in intracellular calcium levels and subsequently initiating the process of Excitation-contraction coupling. (wikipedia.org)