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.Streptococcus pyogenes: A species of gram-positive, coccoid bacteria isolated from skin lesions, blood, inflammatory exudates, and the upper respiratory tract of humans. It is a group A hemolytic Streptococcus that can cause SCARLET FEVER and RHEUMATIC FEVER.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.Streptococcal Infections: Infections with bacteria of the genus STREPTOCOCCUS.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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Cardiac myocytes express two types of voltage operated calcium currents, a high voltage activated (HVA) L-type, and a low voltage activated (LVA) T-type. Influx of calcium into the cell through the L-type channel is responsible for excitation-contraction coupling in the heart. The T-type calcium current has been associated with growth and differentiation in a number of different cell types. An atrial myocyte cell line (HL-1) that selectively expresses T-type calcium current was employed to show that inhibiting calcium influx through the T-type calcium channel inhibits cellular proliferation. Drug dosage studies demonstrate that the T-type calcium channel responsible for this effect is Cav 3.1. Furthermore, blocking the calcium influx through the T-type calcium channel arrests cells in the G2/M phase of the cell cycle. Interestingly, the proliferative effect of calcium influx through the T-type calcium channel appears to happen in the early G1 phase of the cell cycle ...
TY - JOUR. T1 - Synthesis and biological evaluation of 1-(2-hydroxy-3-phenyloxypropyl) piperazine derivatives as T-type calcium channel blockers. AU - Park, Jung Eun. AU - Ji, Wan Keun. AU - Jang, Jae Wan. AU - Pae, Ae Nim. AU - Choi, Keehyun. AU - Choi, Kihang. AU - Kang, Jahyo. AU - Roh, Eun Joo. PY - 2013/3/15. Y1 - 2013/3/15. N2 - To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 2-hydroxy-3-phenoxypropyl piperazine derivatives were synthesized and evaluated for in vitro activities. Compound 6m and 6q showed high selectivity over hERG channel (IC50 ratio of hERG/α1G 6m = 8.5, 6q = 18.38) and they were subjected to measure pharmacokinetics profiles. Among them compound 6m showed an excellent pharmacokinetic profile in rats.. AB - To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 2-hydroxy-3-phenoxypropyl piperazine derivatives were synthesized and evaluated for in vitro activities. Compound 6m and ...
4-Fluoro-Piperidine T-Type Calcium Channel Antagonists - The present invention is directed to 4-fluoro-piperidine compounds which are antagonists of T-type calcium channels, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which T-type calcium channels are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels are involved ...
Here, we report the novel findings that in human adrenal glomerulosa cells both basal and stimulated rates of aldosterone production depend on voltage-gated calcium currents through T-type as well as L-type calcium channels. These findings are surprising because patch-clamp studies consistently report the basal membrane potential of ZG cells to be very hyperpolarized (around −80 mV), a potential at which high threshold L-type calcium channels are not expected to be active. In contrast, low threshold T-type calcium channels are activated at more hyperpolarized potentials and have a permissive window of steady-state activity at more hyperpolarized potentials (Perez-Reyes 2003). When stimulated by low physiological concentrations of Ang II or small increases in extracellular potassium, the membrane potential of ZG cells can rapidly reach the permissive voltage window for persistent T-type, but not L-type, calcium channel activity, that allows steady-state calcium influx (Rossier 2016). Therefore, ...
1. A method for preventing or treating hypercardia, heart failure, cardiomyopathy, atrial fibrillation, tachyarrhythmia, arterial sclerosis, nephritis, nephropathy, renal disorder, renal insufficiency, inflammation, edema, hyper-aldosteronism, neurogenic pain, epilepsy or cancer, comprising:administering to a subject in need thereof an effective amount of a T-type calcium channel blocker having a nitrogen-containing hetero ring moiety of formula (1) ##STR00015## or a pharmaceutically acceptable salt thereof,wherein Ar1 of formula (1) is a substituent selected from the group consisting of a phenyl group, a pyridyl group, a furyl group or a 2,1,3-benzoxadiazol-4-yl group;wherein the Ar1 substituent may be optionally substituted with one or two substituents selected from the group consisting of NO2, CF3, Br, Cl, F, C1-20 alkyl group, OH, OR6, OCHF2, COOR6, NH2, NHR6, NR6R7, CONH2, CONHR6, CONR6R7, COSR6, SR6, S(O)R6, S(O)2R6, SO3H, SO3R6, SO2NH2, SO2NHR6, SO2NR6R7, CN and phenyloxy group, ...
T-type calcium channels and cannabinoid receptors are known to play important roles in chronic pain, making them attractive therapeutic targets. We recently reported on the design, synthesis and analgesic properties of a novel T-type channel inhibitor (NMP-7), which also shows mixed agonist activity on CB1 and CB2 receptors in vitro. Here, we analyzed the analgesic effect of systemically delivered NMP-7 (intraperitoneal (i.p.) or intragstric (i.g.) routes) on mechanical hypersensitivity in inflammatory pain induced by Complete Freunds Adjuvant (CFA) and neuropathic pain induced by sciatic nerve injury. NMP-7 delivered by either i.p. or i.g. routes produced dose-dependent inhibition of mechanical hyperalgesia in mouse models of inflammatory and neuropathic pain, without altering spontaneous locomotor activity in the open-field test at the highest active dose. Neither i.p. nor i.g. treatment reduced peripheral inflammation per se, as evaluated by examining paw edema and myeloperoxidase activity. The
The T-type Ca2+ channel Cav3.2 is expressed in nociceptive and mechanosensitive sensory neurons. The mechanosensitive D-hair (down-hair) neurons, which innervate hair follicles, are characterized by a large-amplitude Cav3.2 T-current involved in the amplification of slow-moving stimuli. The molecules and signalling pathways that regulate T-current expression in mechanoreceptors are unknown. In the present study, we investigated the effects of NT-4 (neurotrophin-4) on Cav3.2 T-current expression in D-hair neurons in vitro. Interruption of the supply of NT-4 with peripheral nerve axotomy induced a non-transcriptional decrease in the T-current amplitude of fluorogold-labelled axotomized sensory neurons. The T-current amplitude was restored by incubation with NT-4. Deletion of NT-4 through genetic ablation resulted in a similar selective loss of the large-amplitude T-current in NT-4−/− sensory neurons, which was rescued by the addition of NT-4. NT-4 had no effect on the T-current in ...
They found that neurons showed an increase in viability after treatment with either L-type or T-type calcium channel inhibitors. Furthermore, neurons in the long-term and short-term cultures were protected, respectively, by L-type and T-type calcium channel blockers, suggesting that more than one calcium-signaling mechanism exists to regulate long- and short-term neuron survival.. There are presently no effective medications for age-related neurodegeneration. Bao said "Our data provides implications for the use of this family of anti-epileptic drugs in developing new treatments for neuronal injury, and for the need of further studies of the use of such drugs in age-related neurodegenerative disorders.". 1. Neuroprotective effects of blockers for T-type calcium channels ...
The aim of this study was to use an established thalamocortical computer model to determine how T-type calcium channels work in concert with cortical excitability to contribute to pathogenesis and treatment response in CAE. METHODS: The model is comprised of cortical pyramidal, cortical inhibitory, thalamocortical relay, and thalamic reticular single-compartment neurons, implemented with Hodgkin-Huxley model ion channels and connected by AMPA, GABAA , and GABAB synapses. Network behavior was simulated for different combinations of T-type calcium channel conductance, inactivation time, steady state activation/inactivation shift, and cortical GABAA conductance. RESULTS: Decreasing cortical GABAA conductance and increasing T-type calcium channel conductance converted spindle to spike and wave oscillations; smaller changes were required if both were changed in concert. In contrast, left shift of steady state voltage activation/inactivation did not lead to spike and wave oscillations, whereas right ...
Despite a growing body of evidence implicating T-channels in nociception (Todorovic et al., 2001; Bourinet et al., 2005; Choi et al., 2007), the cellular and molecular basis of their function in nociceptors is poorly understood. In the present study, we demonstrated that reducing agents sensitize nociceptors both in vitro and in vivo in a manner that is dependent on Cav3.2. In current-clamp experiments on acutely dissociated rat DRG neurons, we show that l-cys lowers the threshold for excitability in C-type cells that express Cav3.2 currents but not in C-type cells expressing only HVA Ca2+ currents. Furthermore, we show that a similar form of sensitization is present in Cav3.2 current-containing, C-type nociceptors from wild-type mice but not from Cav3.2−/− mice. Additionally, we demonstrated that reducing agents induce thermal sensitization when injected into peripheral receptive fields in vivo, in which putative Cav3.2 channels are located on nociceptor endings. Importantly, this ...
The voltage-activated T-type calcium channel (CaV3.2) and the G protein-coupled neurokinin 1 (NK1) receptor are expressed in peripheral tissues and in central neurons where they participate in diverse physiological processes including neurogenic inflammation and nociception. In the present report, we demonstrate that recombinant CaV3.2 channels are reversibly inhibited by NK1 receptors when both proteins are transiently coexpressed in human embryonic kidney (HEK293) cells. We found that the voltage-dependent macroscopic properties of CaV3.2 currents were unaffected during NK1 receptor-mediated inhibition. However, inhibition was attenuated in cells coexpressing either the dominant-negative Gαq Q209L/D277N or the regulator of G protein signaling proteins 2 (RGS2) and 3T (RGS3T) which are effective antagonist of Gαq/11. By contrast, inhibition was unaffected in cells coexpressing human rod transducin (Gαt), which buffers Gβγ. Channel inhibition was blocked by U73122 and bisindolylmaleimide I, ...
Correspondence should be addressed to either of the following: Terence OBrien, Department of Medicine (Royal Melbourne Hospital/Western Hospital), The University of Melbourne, 4th Floor, Clinical Sciences Building, Royal Melbourne Hospital, Royal Parade, Parkville, Victoria 3050, Australia, obrientj{at}unimelb.edu.au; or Terrance Snutch, Michael Smith Laboratories, The University of British Columbia, 301-2185 East Mall, Vancouver, British Columbia, Canada V6T 1Z4, snutch{at}msl.ubc.ca ...
Local signals maintain mature stem cells in lots of tissues. differentiated somatic cells in the adult mammalian testis but its rules isnt well realized. Our work shows that sex maintenance happens in adult somatic stem cells and that highly conserved procedure can be governed by effectors of market signals. Introduction Man versus female destiny is managed by a number of systems across taxa (Kopp 2012 In mammals this choice was lately found to become labile actually in adults; lack of sex-specific transcriptional regulators in the adult mouse gonad causes differentiated somatic cells to transdifferentiate into somatic cells of the contrary sex Resveratrol (Matson et al. 2011 Uhlenhaut et al. 2009 This means that that sexual identification must continuously become maintained in particular differentiated cell types lengthy after sex dedication has happened. Whether sexual identification is plastic material in undifferentiated adult stem cells continues to be unfamiliar. Since adult stem cells ...
Using the video imaging technique this group has previously reported that regulatory volume decrease (RVD) in ZR-75-1 cells is Ca2+ dependent. RVD was inhibited in the absence of external Ca2+ and in the presence of voltage-gated Ca2+ channel inhibitors, nifedipine (L-type) and flunarizine (T-type; Ashes et al. 2002). These results suggested that external Ca2+ entered the cell via voltage-gated L- and/or T-type Ca2+ channels. In this study, the expression of L- and T-type channels was investigated in ZR-75-1 cells using reverse transcriptase-polymerase chain reaction (RT-PCR). The α1C and α1D are subunits of the L-type Ca2+ channel. The α1C subunit is expressed in cardiac muscle and the α1D subunit in the CNS and endocrine cells, where it may have a role in stimulus-secretion coupling. The α1G, α1H and α1I subunits have been cloned and display biophysical and pharmacological properties of native T-type Ca2+ channels when overexpressed in Xenopus oocytes or HEK-293 cells (Randall & Benham ...
Numerous investigations reported that increases of internal Ca2+ (Ca2+i) pivotally regulate high voltage-activated (HVA) Ca2+ channels via calmodulin (CaM). However, it is largely elusive that Ca2+i can regulate low voltage-activated T-type Ca2+ channels. Using whole cell patch clamp, we compared the biophysical properties of Ca2+ current through T-type Ca2+ channel Cav3.1, Cav3.2, or Cav3.3 stably expressed in HEK293 cells between internal solutions containing 27 nM and l μM free Ca2+. Both activation and inactivation kinetics of Cav3.3 current in l μM Ca2+i solution were more rapid than those of Cav3.3 in 27 nM Ca2+i solution. In addition, both activation and steady-state inactivation curves of Cav3.3 were negatively shifted in the higher Ca2+i solution. In contrast, the biophysical properties of Cav3.1 and Cav3.2 isoforms were not different between the two internal solutions. Overexpression of CaM1234 (calmodulin mutant lacking 4 Ca2+ binding sites) strongly suppressed the effects of l μM ...
This gene encodes the pore-forming alpha subunit of a voltage gated calcium channel. The encoded protein is a member of a subfamily of calcium channels referred to as is a low voltage-activated, T-type, calcium channel. The channel encoded by this protein is characterized by a slower activation and inactivation compared to other T-type calcium channels. This protein may be involved in calcium signaling in neurons. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]
Glioblastoma (GBM) stem-like cells (GSC) promote tumor initiation, progression, and therapeutic resistance. Here, we show how GSCs can be targeted by the FDA-approved drug mibefradil, which inhibits the T-type calcium channel Cav3.2. This calcium channel was highly expressed in human GBM specimens and enriched in GSCs. Analyses of the The Cancer Genome Atlas and REMBRANDT databases confirmed upregulation of Cav3.2 in a subset of tumors and showed that overexpression associated with worse prognosis. Mibefradil treatment or RNAi-mediated attenuation of Cav3.2 was sufficient to inhibit the growth, survival, and stemness of GSCs and also sensitized them to temozolomide chemotherapy. Proteomic and transcriptomic analyses revealed that Cav3.2 inhibition altered cancer signaling pathways and gene transcription. Cav3.2 inhibition suppressed GSC growth in part by inhibiting prosurvival AKT/mTOR pathways and stimulating proapoptotic survivin and BAX pathways. Furthermore, Cav3.2 inhibition decreased ...
Choe W, Messinger RB, Leach E, Eckle VS, Obradovic A, Salajegheh R, Jevtovic-Todorovic V, Todorovic SM. TTA-P2 is a potent and selective blocker of T-type calcium channels in rat sensory neurons and a novel antinociceptive agent. Mol Pharmacol. 2011;80:900-10 ...
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Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown. However, using cell-based assays and integrated proteomics, phosphoproteomics, and transcriptomics analyses, we identified the downstream signaling events these drugs affect. Changes in plasma membrane depolarization and elevated intracellular Na+, which compromised Na+-dependent nutrient transport, were documented. Deficits in nutrient deficit acted in turn to trigger the unfolded protein response and the amino acid response, leading ultimately to nutrient starvation and GIC cell death. ...
DePuy SD, Yao J, Hu C, McIntire W, Bidaud I, Lory P, Rastinejad F, Gonzalez C, Garrison JC, Barrett PQ. The molecular basis for T-type Ca2+ channel inhibition by G protein beta2gamma2 subunits. Proc Natl Acad Sci U S A. 2006 Sep 26; 103(39):14590-5 ...
Participation of low-threshold calcium spikes in excitatory synaptic transmission in guinea pig medial frontal cortex.: We studied the activation of low-thresho
Regulation of low-voltage activated T-type Ca2+ channel activity by kinases and heterotrimeric G-proteins and their roles in physiological responses.. ...
Ca2+ influx through voltage-dependent Ca2+ channels regulates vascular remodeling and contraction. However, the role of T-type Ca2+ channels (TCCs) has remained unknown in the ductus arteriosus (DA). Here we hypothesized that Ca2+ influx via TCC contributed to DA closure through promoting neointimal cushion formation and oxygen-induced vascular contraction. Quantitative RT-PCR analysis revealed that α1G, a TCC subtype, was significantly up-regulated in rat neonatal DA tissues at birth and in DA smooth muscle cells (SMCs) that were exposed to oxygen. The expression of α1G mRNA was higher in DA than in the aorta. Immunohistlogical analysis revealed that α1G was localized predominantly to the region of intimal thickening in fetal DA at term and to the central core of neonatal DA at birth. To examine the effects of blockade of TCCs, we used α1G-specific siRNA or R(−)-efonidipine, a highly selective TCC blocker that was recently developed. α1G-specific siRNAs inhibited SMC migration by 55% ...
The present study provides 2 major new findings. First, in contrast to its peripheral effects, centrally administered nifedipine decreases RSNA and HR in conscious SHR. Second, these sympathoinhibitory effects of nifedipine are enhanced in SHR on high versus regular sodium intake.. Dihydropyridine-sensitive, low-voltage-activated calcium channels have been demonstrated in rat brain neurons freshly isolated from regions such as the ventromedial hypothalamus.6 The role of the different types of calcium channels in neuronal synaptic transmission has not been clarified. In rat hippocampal cells,7 during neuronal activation postsynaptic or presynaptic Ca2+ entry involves the activation of the P/Q-, L-, or N-type Ca2+ channels but not the T-type Ca2+ channels. Unless dissolved in certain solvents such as dimethylsulfoxide,15 nifedipine blocks only L-type channels and has no effects on T-type channels in neuronal cells.8 15 In the present study nifedipine was dissolved in a vehicle containing no ...
Frequency of genetic polymorphism of calcium channels gene CACNA1C in healthy individuals and patients with arterial hypertension
When neuronal activity is reduced over a period of days, compensatory changes in synaptic strength and/or cellular excitability are triggered, which are thought to act in a manner to homeostatically recover normal activity levels. The time course over which changes in homeostatic synaptic strength and cellular excitability occur are not clear. Although many studies show that 1-2 days of activity block are necessary to trigger increases in excitatory quantal strength, few studies have been able to examine whether these mechanisms actually underlie recovery of network activity. Here, we examine the mechanisms underlying recovery of embryonic motor activity following block of either excitatory GABAergic or glutamatergic inputs in vivo. We find that GABAA receptor blockade triggers fast changes in cellular excitability that occur during the recovery of activity but before changes in synaptic scaling. This increase in cellular excitability is mediated in part by an increase in sodium currents and a reduction
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The combination of the nonspecific F-type channels and the closing of K+ channels results in a steady depolarization when membrane potential is negative, these channels paired with the effects of T-type Ca+2 channels allow recurring depolarization following repolarization and therefore facilitate the pacemaker ...
Analysis of the Wtb vertex from the measurement of triple-differential angular decay rates of single top quarks produced in the t-channel at $\sqrt{s}=8$ TeV with the ATLAS detector / M. Aaboud, [et al.], L. ADAMCZYK, [et al.], T. BOŁD, [et al.], W. DĄBROWSKI, [et al.], G. P. GACH, [et al.], I. GRABOWSKA-BOŁD, [et al.], M. P. GUZIK, [et al.], P. A. JANUS, [et al.], D. KISIELEWSKA, [et al.], S. KOPERNY, [et al.], T. Z. KOWALSKI, [et al.], J. A. KREMER, [et al.], B. MINDUR, [et al.], M. PRZYBYCIEŃ, [et al.], A. ZEMŁA, [et al.] // The Journal of High Energy Physics ; ISSN 1126-6708. - 2017 iss. 12 art. no. 017, s. [1], 1-59. - Bibliogr. s. 37-42, Abstr.. - Publikacja dostępna online od: 2017-12-04. - tekst: https://goo.gl/XXSNDX ...
A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous as voltage-gated calcium channel, although there are also ligand-gated calcium channels. The following tables explain gating, gene, location and function of different types of calcium channels, both voltage and ligand-gated. the receptor-operated calcium channels (in vasoconstriction) P2X receptors L-type calcium channel blockers are used to treat hypertension. In most areas of the body, depolarization is mediated by sodium influx into a cell; changing the calcium permeability has little effect on action potentials. However, in many smooth muscle tissues, depolarization is mediated primarily by calcium influx into the cell. L-type calcium channel blockers selectively inhibit these action potentials in smooth muscle which leads to dilation of blood vessels; this in turn corrects hypertension. T-type calcium channel blockers are used to treat epilepsy. Increased calcium conductance in ...
Injection of NMDAR antagonist into the thalamus can produce delta frequency EEG oscillations in the thalamocortical system. It is surprising that an antagonist of an excitatory neurotransmitter should trigger such activity, and the mechanism is unknown. One hypothesis is that the antagonist blocks excitation of GABAergic cells, thus producing disinhibition. To test this hypothesis, we investigated the effect of NMDAR antagonist (APV) on cells of the nucleus reticularis (nRT) in rat brain slices, a thalamic nucleus that can serve as a pacemaker for thalamocortical delta oscillations and that is composed entirely of GABAergic neurons. We found, unexpectedly, that nRT cells are hyperpolarized by APV. This occurs because these cells have an unusual form of NMDAR (probably NR2C) that contributes inward current at resting potential in response to ambient glutamate. The hyperpolarization produced by APV is sufficient to deinactivate T-type calcium channels, and these trigger rhythmic bursting at delta
ID F7H6P3_MACMU Unreviewed; 2291 AA. AC F7H6P3; DT 27-JUL-2011, integrated into UniProtKB/TrEMBL. DT 30-NOV-2016, sequence version 2. DT 25-OCT-2017, entry version 36. DE RecName: Full=Voltage-dependent T-type calcium channel subunit alpha {ECO:0000256,RuleBase:RU003808}; GN Name=CACNA1G {ECO:0000313,Ensembl:ENSMMUP00000034848}; OS Macaca mulatta (Rhesus macaque). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Cercopithecidae; Cercopithecinae; Macaca. OX NCBI_TaxID=9544 {ECO:0000313,Ensembl:ENSMMUP00000034848, ECO:0000313,Proteomes:UP000006718}; RN [1] {ECO:0000313,Ensembl:ENSMMUP00000034848, ECO:0000313,Proteomes:UP000006718} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=17573 {ECO:0000313,Ensembl:ENSMMUP00000034848, RC ECO:0000313,Proteomes:UP000006718}; RX PubMed=17431167; DOI=10.1126/science.1139247; RA Gibbs R.A., Rogers J., Katze M.G., Bumgarner R., Weinstock G.M., RA Mardis ...
ID I3N0U5_ICTTR Unreviewed; 1770 AA. AC I3N0U5; DT 11-JUL-2012, integrated into UniProtKB/TrEMBL. DT 11-JUL-2012, sequence version 1. DT 27-SEP-2017, entry version 37. DE RecName: Full=Voltage-dependent T-type calcium channel subunit alpha {ECO:0000256,RuleBase:RU003808}; GN Name=CACNA1I {ECO:0000313,Ensembl:ENSSTOP00000017991}; OS Ictidomys tridecemlineatus (Thirteen-lined ground squirrel) OS (Spermophilus tridecemlineatus). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciuromorpha; OC Sciuridae; Xerinae; Marmotini; Ictidomys. OX NCBI_TaxID=43179 {ECO:0000313,Ensembl:ENSSTOP00000017991, ECO:0000313,Proteomes:UP000005215}; RN [1] {ECO:0000313,Ensembl:ENSSTOP00000017991} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RG The Broad Institute Genome Assembly & Analysis Group; RG Computational R&D Group; RG and Sequencing Platform; RA Di Palma F., Alfoldi J., Johnson J., Berlin A., Gnerre S., Jaffe D., RA MacCallum ...
학술회의] 민철기, Hae-Kwon Kim, Jae-Ho Lee, Yun-Jin Jung, Kyoo Wan Choi, Seung-Jae Lee, Sung Eun Lee, Hwa Lee Ryu, Ju-Hee Lee, Inhibitory action of mibefradil on steroidogenesis in mouse leydig cells: involvement of Ca+2 entry through T-type Ca+2 channels in steroidogenesis , ESHRE 21st Annual Meeting , Vol.21 , pp.121 -121 (Jun, 2005) ...
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[button size=small text=MSDS & Datasheet link=/wp-content/uploads/media/BCDatasheets_C_10.26/IXXXX/I-7201-1.pdf]Ferritin Conjugated Cancer antenn
References for Abcams Recombinant Human CA8 protein (ab123192). Please let us know if you have used this product in your publication
TY - JOUR. T1 - Ca2+ channel subtypes and pharmacology in the kidney. AU - Hayashi, Koichi. AU - Wakino, Shu. AU - Sugano, Naoki. AU - Ozawa, Yuri. AU - Homma, Koichiro. AU - Saruta, Takao. PY - 2007/2/1. Y1 - 2007/2/1. N2 - A large body of evidence has accrued indicating that voltage-gated Ca channel subtypes, including L-, T-, N-, and P/Q-type, are present within renal vascular and tubular tissues, and the blockade of these Ca channels produces diverse actions on renal microcirculation. Because nifedipine acts exclusively on L-type Ca channels, the observation that nifedipine predominantly dilates afferent arterioles implicates intrarenal heterogeneity in the distribution of L-type Ca channels and suggests that it potentially causes glomerular hypertension. In contrast, recently developed Ca channel blockers (CCBs), including mibefradil and efonidipine, exert blocking action on L-type and T-type Ca channels and elicit vasodilation of afferent and efferent arterioles, which suggests the ...
Dopaminergic neurons of the substantia nigra pars compacta (SNc) are involved in the control of movement, sleep, reward, learning, and nervous system disorders and disease. To date, a thorough characterization of the ion channel phenotype of this important neuronal population is lacking. Using immunohistochemistry, we analyzed the somatodendritic expression of voltage-gated ion channel subunits that are involved in pacemaking activity in SNc dopaminergic neurons in 6-, 21-, and 40-day-old rats. Our results demonstrate that the same complement of somatodendritic ion channels is present in SNc dopaminergic neurons from P6 to P40. The major developmental changes were an increase in the dendritic range of the immunolabeling for the HCN, T-type calcium, Kv4.3, delayed rectifier, and SK channels. Our study sheds light on the ion channel subunits that contribute to the somatodendritic delayed rectifier (Kv1.3, Kv2.1, Kv3.2, Kv3.3), A-type (Kv4.3) and calcium-activated SK (SK1, SK2, SK3) potassium ...
At supratherapeutic doses (2- to 5-fold), the T-type Ca2+antagonist mibefradil modifies the T/U wave of the human ECG. In this study, we show that this effect is observed in conscious monkeys and is duplicated by verapamil or diltiazem. We then evaluate the proarrhythmic risk of such alterations of cardiac repolarization by examining the actions of mibefradil on cardiac action potentials (APs). In isolated cardiomyocytes from guinea pigs or humans, mibefradil dose dependently shortens the plateau of the AP; this effect is similar to other Ca2+ antagonists and opposite to drugs having class III antiarrhythmic properties. The metabolites of mibefradil, singly or in combination, also shorten APs. In isolated rabbit hearts, noncardiodepressant concentrations of mibefradil have no effect on monophasic action potentials (MAPs), whereas cardiodepressant levels produce a slight nonsignificant lengthening. In hearts of open-chest bradycardic dogs, mibefradil has no effect on MAP dispersion or on QT ...
Efonidipine (INN) is a dihydropyridine calcium channel blocker marketed by Shionogi & Co. of Japan. It was launched in 1995, under the brand name Landel. The drug blocks both T-type and L-type calcium channels. It has also been studied in atherosclerosis and acute renal failure.
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Mouse monoclonal antibody raised against a full-length recombinant CA13. CA13 (NP_940986.1, 1 a.a. ~ 262 a.a) full-length recombinant protein with GST tag. MW of the GST tag alone is 26 KDa. (H00377677-M) - Products - Abnova
Contractions induced by 10 nM endothelin-1 (ET) in the rabbit aortic media intimal layer were inhibited by prior exposure to 100 microM Ni++ (33.1%) or to a Ca(++)-free buffer (80.2%) but were unaffected by pretreatment with 0.1 microM nifedipine. Contractions elicited by phenylephrine (1 nM-100 microM) or K+ (10-50 mM) were not inhibited by 100 microM Ni++ but those induced by ET in tissues submaximally precontracted with 20 mM K+ were selectively antagonized by the divalent cation. The mechanism for the inhibitory action of Ni++ was ascertained by an examination of the effects of the cation on ET-induced alterations in the cellular distribution and mobilization of Ca++. Efflux of 45Ca from the muscle into a solution without added Ca++ was not altered by ET. Total or cellular 45Ca uptake (uptake after exposure to La and low temperature), at either low- or high-affinity sites in resting muscles was also not affected by the peptide. However, low-affinity cellular 45Ca retention in muscles ...
White bass (Roccus chrysops) retinal horizontal cells possess two types of voltage-activated calcium currents which have recently been characterized with regard to their voltage dependence and pharmacology (Sullivan, J., and E. M. Lasater. 1992. Journal of General Physiology. 99:85-107). A low voltage-activated transient current was identified which resembles the T-type calcium current described in a number of other preparations, along with a sustained high threshold, long-lasting calcium current that resembles the L-type calcium current. Here we report on the modulation of horizontal cell calcium channels by dopamine. Under whole-cell voltage clamp conditions favoring the expression of both calcium currents, dopamine had opposing actions on the two types of voltage-sensitive calcium currents in the same cone-type horizontal cell. The L-type calcium current was significantly potentiated by dopamine while the T-type current was simultaneously reduced. Dopamine had no effect on calcium currents in ...
The R-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α1 subunit forms the pore through which calcium enters the cell and determines most of the channels properties. This α1 subunit is also known as the calcium channel, voltage-dependent, R type, alpha 1E subunit (CACNA1E) or Cav2.3 which in humans is encoded by the CACNA1E gene. They are strongly expressed in cortex, hippocampus, striatum, amygdala and interpeduncular nucleus. They are poorly understood, but like Q-type calcium channels, they appear to be present in cerebellar granule cells. They have a high threshold of activation and relatively slow kinetics. "Entrez Gene: CACNA1E calcium channel, voltage-dependent, R type, alpha 1E subunit". Soong TW, Stea A, Hodson CD, Dubel SJ, Vincent SR, Snutch TP (May 1993). "Structure and functional expression of a member of the low voltage-activated calcium channel family". Science. 260 (5111): 1133-6. doi:10.1126/science.8388125. PMID ...
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 ...
Low-voltage-activated calcium channels in the lamprey locomotor network: simulation and experiment. J. Neurophysiol. 77: 1795-1812, 1997. To evaluate the role of low-voltage-activated (LVA) calcium channels in the lamprey spinal locomotor network, a previous computer simulation model has been extended to include LVA calcium channels. It is also of interest to explore the consequences of a LVA conductance for the electrical behavior of the single neuron. The LVA calcium channel was modeled with voltage-dependent activation and inactivation using the m 3 h form, following a Hodgkin-Huxley paradigm. Experimental data from lamprey neurons was used to provide parameter values of the single cell model. The presence of a LVA calcium conductance in the model could account for the occurrence of a rebound depolarization in the simulation model. The influence of holding potential on the occurrence of a rebound as well the latency at which it is elicited was investigated and compared with previous ...
Background- Pharmacological interventions for prevention of sudden arrhythmic death in patients with chronic heart failure remain limited. Accumulating evidence suggests increased ventricular expression of T-type Ca2+ channels contributes to the progression of heart failure. The ability of T-type Ca2+ channel blockade to prevent lethal arrhythmias associated with heart failure has never been tested, however.. Methods and Results- We compared the effects of efonidipine and mibefradil, dual T- and L-type Ca2+ channel blockers, with those of nitrendipine, a selective L-type Ca2+ channel blocker, on survival and arrhythmogenicity in a cardiac-specific, dominant-negative form of neuron-restrictive silencer factor transgenic mice (dnNRSF-Tg), which is a useful mouse model of dilated cardiomyopathy leading to sudden death. Efonidipine, but not nitrendipine, substantially improved survival among dnNRSF-Tg mice. Arrhythmogenicity was dramatically reduced in dnNRSF-Tg mice treated with efonidipine or ...
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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 ...
volume of conference proceedings reviews the general pathophysiological significance of the isoforms of cyclooxygenase, and the likely value of selective COX-2 inhibitors in the treatment of rheumatoid conditions. Also covered is the possible use of antibodies against cytokines and cell adhesion receptors in the treatment of inflammatory conditions.
My colleague Holt Hedrick has posted some interesting thoughts on the B&T Currents blog about the NLRBs decision not to appeal to the Supreme Court, its decision in
A 74 frissen felismert g nvari ci r l, amelyek n velhetik a hormonokkal kapcsolatos h rom r kt pus kialakul s t, m rcius 27- n sz moltak be.
Liao, P., Yu, D., Li, G., Tan, F.Y., Tuck, W.S., Jia, L.S., Yeow, L.C. (2007). A smooth muscle Cav1.2 calcium channel splice variant underlies hyperpolarized window current and enhanced state-dependent inhibition by nifedipine. Journal of Biological Chemistry 282 (48) : 35133-35142. [email protected] Repository. https://doi.org/10.1074/jbc. ...
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.
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.
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
Can anyone recommend any newsgroups dealing with calcium channel of SR? Thank you in advance for your help. ssultang (in english, sugar ...
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View mouse Cacna1s Chr1:136052805-136119822 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
... - The Crestron CNXRY installs in any Y-Bus expansion slot of a 2-Series control system to provide 16 isolated, low-voltage relay closures. Each group of
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
Reagents and test methods for rapidly and specifically testing maize plants for the presence of T-type cms are provided. The reagent includes a novel nucleic acid segment whose sequence is uniquely arranged in mitochondrial DNA of cms-T maize. The segment, designated TURF 2H3, was cloned and vectors comprising TURF 2H3 provided. Subclones having sequences specific to cms-T mitochondrial DNA and the DNA and deduced amino acid sequences of ORI3, which is unique to T-type cytoplasm, are also provided.
Background Psychomotor disturbances have been described repeatedly over many centuries. More recently, Sobin and Sackeim [Sobin, C., Sackeim, H.A., 1997. Psychomotor symptoms of depression. Am. J. Psychiatry. 154, 417.] discussed the relevance of psychomotor symptoms in depression in an extensive review. Since their report, new pathophysiological, diagnostic and therapeutic findings have been published. In the current review of the recent literature, we aim to argue the importance of psychomotor symptoms in depression and propose directions for future research. Method A review of all the relevant reports on this topic, published between 1996 and 2006, was conducted. Results Several assessment methods demonstrate the diagnostic and pathophysiological significance of psychomotor symptoms. Antidepressants show differential effects on psychomotor performance and findings concerning the symptoms predictive capacity for clinical response are contradictory. Numerous imaging studies as well as studies ...
CoAA contains two copies of RNA recognition motifs (RRM) and an intrinsic transactivation domain rich in repetitive tyrosines and glutamines (YxxQ domain). Previously, CoAA has been shown to be a transcriptional coactivator that stimulates transcriptional activation and regulates alternative splicing. A pattern and profile search revealed that the YxxQ domain in CoAA shared significant pattern homology with the oncogenic EWS activation domains (EAD) in TET family proteins, including, TLS/FUS, EWS and TAFII 68. It was further demonstrated that CoAAs YxxQ domain and EWS EAD also shared functional similarities. Based on these findings, this work investigated the aberration of CoAA in cancers and its pathophysiological significance. The results showed that the CoAA gene was amplified in a high percentage of inflammation-related human cancers with recurrent loss of the 5 regulatory element upstream of its promoter. This genomic aberration resulted in CoAA protein overexpression, which in turn, ...
CoAA contains two copies of RNA recognition motifs (RRM) and an intrinsic transactivation domain rich in repetitive tyrosines and glutamines (YxxQ domain). Previously, CoAA has been shown to be a transcriptional coactivator that stimulates transcriptional activation and regulates alternative splicing. A pattern and profile search revealed that the YxxQ domain in CoAA shared significant pattern homology with the oncogenic EWS activation domains (EAD) in TET family proteins, including, TLS/FUS, EWS and TAFII 68. It was further demonstrated that CoAAs YxxQ domain and EWS EAD also shared functional similarities. Based on these findings, this work investigated the aberration of CoAA in cancers and its pathophysiological significance. The results showed that the CoAA gene was amplified in a high percentage of inflammation-related human cancers with recurrent loss of the 5 regulatory element upstream of its promoter. This genomic aberration resulted in CoAA protein overexpression, which in turn, ...
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Rabbit polyclonal Two pore calcium channel protein 2 antibody validated for WB, IHC and tested in Human. Immunogen corresponding to synthetic peptide
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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.
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simulation from: Lytton WW; Contreras D; Destexhe A; Steriade M. Dynamic interactions determine partial thalamic quiescence in a computer network model of spike-and-wave seizures. J Neurophysiol, 77:1679-1696, 1997. Fig 7 on p 1688 (jnphys77:1679.pdf) Simulation of figure 7 may take several minutes. fig7.gif shows the output of the simulation. A phase plane analysis of a two cell interaction between a thalamocortical neuron (TC) and a thalamic reticularis neuron (RE). Figure legend : Analysis of spontaneous transition from mutual to quiescent mode with bursting viewed in the RE T-channel m/h plane. A. RE neuron voltage trace (A1) and TC voltage trace (A2) shows 8 bursts of mutual activity followed by switch into the quiescent state. Color for each cycle give the key for the phase planes below. Interburst intervals are depicted in panel Ba. Alternating bursts are shown in panels Bb and Bc. Initial oscillation appears to be approximately period-2 with burst alternating with an interburst ...
The IUPHAR/BPS Guide to Pharmacology. NNC0640 ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs.
Childhood absence epilepsy (CAE) typically requires treatment because the seizures are frequent and interfere with normal cognitive functioning. International
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 ...
In rat paraventricular thalamic nucleus (PVT) neurons, activation of thyrotropin releasing hormone (TRH) receptors enhances neuronal excitability via concurrent decrease in a GIRK-like conductance and opening of a cannabinoid receptor-sensitive transient receptor potential canonical (TRPC)-like conductance. Here we investigated the calcium (Ca2+) contribution to the components of this TRH-induced response. TRH-induced membrane depolarization was reduced in the presence of intracellular BAPTA, also in media containing nominally zero [Ca2+]o, suggesting a critical role for both intracellular Ca2+ release and Ca2+ influx. TRH-induced inward current was unchanged by T-type Ca2+ channel blockade, but was decreased by blockade of high-voltage-activated Ca2+ channels (HVACCs). Both the pharmacologically isolated GIRK-like and the TRPC-like components of the TRH-induced response were decreased by nifedipine and increased by BayK8644, implying Ca2+ influx via L-type Ca2+ channels. Only the TRPC-like ...
This study is comparing the efficacy, tolerability, quality-of-life effects, pharmacodynamics and pharmacokinetics of ethosuximide, lamotrigine and valproic
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
Compare calcium channel, voltage-dependent, L type, alpha 1S subunit ELISA Kits from leading suppliers on Biocompare. View specifications, prices, citations, reviews, and more.
See the corresponding section in the main epilepsy article. The primary goal of treatment of childhood absence epilepsy is to prevent accidental injuries that may occur during seizures. For those with frequent seizures the goal of treatment includes preventing the seizures from interfering with learning at school and other activities of daily life. The goal of treatment with medications for absence seizures is to accomplish the goals above, by eliminating or reducing the frequency of the absence seizures, without causing side-effects more serious than the epilepsy itself. Certain anticonvulsant drugs are used to minimize the number of seizures. Absence seizures appear to respond well to valproic acid (trade name: Depakote), ethosuximide (trade name: Zarontin), and lamotrigine (trade name: Lamictal). Each of these medications has potential side effects, some of them serious. While the most serious side effects are uncommon, a better understanding of the risks and benefits of each of these ...
Childhood Absence Epilepsy is characterized by absence seizures in children between 4-12. Find information to aid in caring for your child or patient.
Patients will receive mibefradil dihydrochloride, which will be dose escalated from 150mg/day until the maximum tolerated dose (MTD) is determined, or until a dose of 350 mg/day is reached using a standard 3 + 3 design. Mibefradil dihydrochloride will be dosed orally in 4 divided doses per day for 17 consecutive days to the MTD. The MTD will be determined according to dose-limiting toxicities (DLTs) graded using the Common Terminology Criteria for Adverse Events version 4.0. Radiation therapy (RT) consists of 5 fractions of 600 centigray (cGy) each, delivered over 2 consecutive weeks for a total dose of 3,000 cGy, using stereotactic, intensity-modulated radiation therapy (IMRT).. The primary endpoint of the study is to determine the MTD of mibefradil dihydrochloride when given with concurrent hypofractionated RT. Secondary and tertiary endpoints include evaluating the efficacy of mibefradil dihydrochloride and RT in terms of progression-free survival (PFS) and overall survival (OS), and to ...
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 ...
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.
Atrial fibrillation (AF), defined by disorganized atrial cardiac rhythm, is the most prevalent cardiac arrhythmia worldwide. Recent genetic studies have highlighted a major heritable component and identified numerous loci associated with AF risk, including the cardiogenic transcription factor genes TBX5, GATA4, and NKX2-5. We report that Tbx5 and Gata4 interact with opposite signs for atrial rhythm controls compared with cardiac development. Using mouse genetics, we found that AF pathophysiology caused by Tbx5 haploinsufficiency, including atrial arrhythmia susceptibility, prolonged action potential duration, and ectopic cardiomyocyte depolarizations, were all rescued by Gata4 haploinsufficiency. In contrast, Nkx2-5 haploinsufficiency showed no combinatorial effect. The molecular basis of the TBX5/GATA4 interaction included normalization of intra-cardiomyocyte calcium flux and expression of calcium channel genes Atp2a2 and Ryr2. Furthermore, GATA4 and TBX5 showed antagonistic interactions on an ...
Autoantibodies against thrombopoietin (TPO) have been implicated in systemic lupus erythaematosus (SLE) thrombocytopoenia.1 2 To investigate their pathophysiological significance, we have evaluated the effect of SLE sera on megakaryocytic colony formation in vitro.. A total of 35 randomly selected SLE sera were initially screened for the presence of antiplatelet antibodies (APAs), using a commercially available assay (PAK12, GTI Diagnostics, Wauksesha, Wisconsin, USA). In all, 16 sera tested positive and were excluded from the analysis. Only sera negative for APAs have been evaluated in the current study, since APAs have been reported to inhibit megakaryopoiesis in vitro.3 Of the remaining 19 samples, 7 tested positive for anti-TPO antibodies and 12 were negative. TPO concentration was then measured by a ...
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 ...
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.
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 ...
Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent…
Generic Isoptin (Verapamil) is in a group of drugs called calcium channel blockers. Generic Isoptin offers highly effective treatment of numerous symptoms and is one of the top prescribed medicatio...
... 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 ...
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 ...
Cheng, R. C., Tikhonov, D. B., & Zhorov, B. S. (2009). Structural model for phenylalkylamine binding to L-type calcium channels ... The drug targets L-type Ca+2 channels, and decreases conduction in cells where Ca+2 is required for action potential upstroke ( ... BRL-32872's class III activity is directed towards the human ether-a-go-go-related gene (hERG) K+ channel.[4] hERG channels are ... 1995). Electrophysiological effect of BRL-32872, a novel antiarrhythmic agent with potassium and calcium channel blocking ...
The antibodies attack the voltage gated calcium channels of the P/Q type.(reference 35) Abnormal activity of this ion channel, ... Mechanism of action can also impair the calcium channels that induce exocytosis of the vesicles. Other ion channels can also be ... The difference is that LEMS is a result of an autoimmune response on the voltage gated calcium channels of the presynaptic ... in intracellular calcium concentration by causing an increase in ion conductance through voltage gated calcium channels. This ...
"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 ...
... (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 ...
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 ...
N-type calcium-channel blocker.. Intrathecal.. Protein binding = 50%; half-life = 2.9-6.5 hours; excretion = urine (,1%).[120] ... 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.. ... Comes in free form and calcium salt; acetic acid derivative.. As per diclofenac.. PO.. No data.. As per diclofenac.. As per ...
"Functional coupling of intracellular calcium and inactivation of voltage-gated Kv1.1/Kvbeta1.1 A-type K+ channels". Proc. Natl ... channel), voltage gated potassium channel HBK1, voltage gated potassium channel subunit Kv1.1, voltage-gated K+ channel HuKI ... potassium channel activity. • delayed rectifier potassium channel activity. • voltage-gated ion channel activity. • GO:0015388 ... Mutations in this gene cause episodic ataxia type 1. See also[edit]. *GABRA3 - a channel subunit which undergoes similar RNA ...
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 ...
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 ( ...
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 ...
... an ionic current through the L-type calcium channel. ...
... is a cardioselective L-type calcium channel blocker. AH-1058 binds to the same sites on the alpha-1 subunit of L-type ... These sites on the alpha-1 subunit differ from the active site of the calcium channel, meaning AH-1058 binds L-type calcium ... L-type calcium channel blockers). Class I antiarrhythmic (sodium channel blocker) characteristics have also been seen, but the ... In addition AH-1058 appears to interact with multiple states of L-type calcium channels (i.e. resting and inactive) to suppress ...
... 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 ...
... modulates zinc permeation through the L-type calcium channel. SLC30A1 downregulates not only Zn++ influx, but also Ca++ ...
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+ ...
It is a calcium channel blocker of the dihydropyridine type. Nifedipine was discovered in 1969 and approved for use in the ... Although nifedipine and other dihydropyridines are commonly regarded as specific to the L-type calcium channel, they also ... L-type Ca2+ channels in rabbit arteriolar smooth muscle store refilling through a pathway not involving L-type Ca2+ channels in ... The use of nifedipine and related calcium channel antagonists was much reduced in response to 1995 trials that mortality was ...
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 ...
"Structure-activity relationships for P-type calcium channel-selective omega-agatoxins". Nat. Struct. Biol. 1 (12): 853-6. doi: ... The mechanism of many spider toxins is through blockage of calcium channels. A remotely related group of atracotoxins operate ... consensus molecular folding of calcium channel blockers". J. Mol. Biol. 250 (5): 659-71. doi:10.1006/jmbi.1995.0406. PMID ... "Three-dimensional solution structure of the calcium channel antagonist omega-agatoxin IVA: ...
... type-1) and atypical (type-2). They are both caused by mutations in CACNA1C, the gene encoding the calcium channel Cav1.2 α ... "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 ...
Giving vasodilators such as nitroglycerin or calcium channel blockers is recommended. Antihistamine and mast cell stabilizers e ... Type II occurs in people with underlying asymptomatic coronary artery disease where an allergic reaction leads to either ... Corticosteroids, antihistamine, vasodilators such as nitroglycerin and calcium channel blockers are given when appropriate.[ ... Type III occurs in the setting of coronary thrombosis (including stent thrombosis) where aspirated thrombus stained with ...
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" ...
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: ...
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 ...
Amlodipine Besylate is a calcium channel blocker drug. It relaxes blood vessels so blood can flow easily. It is also used to ... In this journey we urge you all to join and support us by reporting any type of counterfeiting of any of our products. You can ... prevent certain types of chest pain.. Cadila Pharmaceuticals Limited is one of the top USFDA approved pharmaceutical companies ...
Effects of calcium channel blockers on in vitro platelet function in whole blood using single platelet counting. Thromb Haemost ... Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or ... Fosphenytoin: Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Management: Monitor for phenytoin ... Calcium channel agonists and antagonists: effects of chronic treatment on pituitary prolactin synthesis and intracellular ...
We then theorized that direct activation of rASIC3 by GMQ is possible due the channels interaction with extracellular calcium ... and can be activated by GMQ in the absence of calcium similarly to wild-type rASIC3. Thus, GMQ activation was introduced in ... intracellular domains of rASIC3 and cASIC1 in order to individually isolate the calcium and nonproton ligand effects on channel ... The peripherally located ASIC3 activates with the simple removal of calcium. Additionally, nonproton ligands, like 2-guanidine- ...
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. ...
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 ...
... and R-type Ca2+ channels are replaced by P/Q-type Ca2+ channels with development. In contrast, multiple types of Ca2+ channels ... 1991) N-type and L-type calcium channels are present in nerve growth cones. Numbers increase on synaptogenesis. Dev Brain Res ... Using type-specific Ca2+ channel blocker toxins, we have demonstrated that the contributions of N-type Ca2+ channels to ... Among them, the ω-conotoxin GVIA-sensitive N-type channels and the ω-Aga-IVA-sensitive P/Q-type channels mediate fast synaptic ...
Abstract 16089: Functional Coupling of SK Channels and L-type Calcium Channels in Cardiomyocytes. Xiao-Dong Zhang, Wei Chun ... Abstract 16089: Functional Coupling of SK Channels and L-type Calcium Channels in Cardiomyocytes ... Abstract 16089: Functional Coupling of SK Channels and L-type Calcium Channels in Cardiomyocytes ... Abstract 16089: Functional Coupling of SK Channels and L-type Calcium Channels in Cardiomyocytes ...
Voltage-dependent L-type calcium channel subunit alpha-1C. Q13936. Details. Voltage-dependent L-type calcium channel subunit ... Voltage-dependent L-type calcium channel subunit alpha-1F. O60840. Details. Voltage-dependent L-type calcium channel subunit ... Voltage-dependent L-type calcium channel subunit beta-1. Q02641. Details. Voltage-dependent L-type calcium channel subunit beta ... Voltage-dependent L-type calcium channel subunit beta-3. P54284. Details. Voltage-dependent L-type calcium channel subunit beta ...
Calcium signalling through L-type calcium channels: role in pathophysiology of spinal nociceptive transmission, British Journal ... L-type calcium channels and NMDA receptors: a determinant duo for short-term nociceptive plasticity. Authors. *. Pascal Fossat, ... Shohei Yamamoto, Yuma Suzuki, Hideki Ono, Kazuhiko Kume, Masahiro Ohsawa, N- and L-type calcium channels blocker cilnidipine ... Cav1.2 and Cav1.3 L-type calcium channels independently control short- and long-term sensitization to pain, The Journal of ...
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 ...
T-type Cav3.1 channels augment nitric oxide and co-localize with eNOS. Therefore, the hypothesis... ... T-type Cav3.1 channels augment nitric oxide and co-localize with eNOS. Therefore, the hypothesis was that T-type channels ... and T-type calcium channels in local and remote calcium responses in rat mesenteric terminal arterioles. J Vasc Res 46:138-151 ... Deletion of T-type calcium channels Cav3.1 or Cav3.2 attenuates endothelial dysfunction in aging mice. ...
Reversal of Neuropathic Pain in Diabetes by Targeting Glycosylation of Cav3.2 T-Type Calcium Channels. ... Reversal of Neuropathic Pain in Diabetes by Targeting Glycosylation of Cav3.2 T-Type Calcium Channels ... Reversal of Neuropathic Pain in Diabetes by Targeting Glycosylation of Cav3.2 T-Type Calcium Channels ... Reversal of Neuropathic Pain in Diabetes by Targeting Glycosylation of Cav3.2 T-Type Calcium Channels ...
Barium-induced secretion was inhibited by the L-type calcium-channel blocker, ... Blockade of potassium channels with barium chloride (5 mM) increased the release of CCK by 374.6 +/- 46.6% of control levels. ... To examine the role of calcium channels in depolarization-activated cholecystokinin (CCK) release, studies were performed in an ... To further evaluate a role for L-type calcium channels in the secretion of CCK, the effects of the L-type calcium channel ...
Reducing agents sensitize C-type nociceptors by relieving high-affinity zinc inhibition of T-type calcium channels J Neurosci ... New evidence that both T-type calcium channels and GABAA channels are responsible for the potent peripheral analgesic effects ... Recent studies have highlighted the importance of T-type calcium channels (T-channels) in peripheral nociception; therefore, ... Silencing of the Cav3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception EMBO J 2005; ...
Two types of calcium channels in single smooth muscle cells from rabbit ear artery studies with whole-cell and single-channel ... Single L-Type Calcium Channels in Smooth Muscle Cells From Resistance Arteries of Spontaneously Hypertensive Rats. Yusuke Ohya ... which inactivated the T-type Ca2+ channels as well as Na+ channels10; and (3) the channel opening disappeared with the ... Single-channel conductance of L-type Ca2+ channels was about 20 pS in both SHR and WKY. We used 50 mmol/L Ba2+ to record the ...
  • 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)
  • We generated a chimeric ASIC combining the extracellular, transmembrane, and intracellular domains of rASIC3 and cASIC1 in order to individually isolate the calcium and nonproton ligand effects on channel activation. (unt.edu)
  • Taken together, we identified that channel state influences nonproton ligand interaction with ASICs, and the transmembrane domains are critical for this interaction. (unt.edu)
  • We then theorized that direct activation of rASIC3 by GMQ is possible due the channel's interaction with extracellular calcium, and were interested in introducing feature into the cASIC1 channel. (unt.edu)
  • Acid-sensing ion channels (ASICs) are trimeric, sodium-selective channels activated by extracellular protons. (unt.edu)
  • A pair of glutamates in rat ASIC3 (E79 and E423) responsible for GMQ activation is present in ASIC1, despite having no direct modulation effect on the channel. (unt.edu)
  • The peripherally located ASIC3 activates with the simple removal of calcium. (unt.edu)
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