Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Inositol 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.Calcium Channels, L-Type: Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.Calcium Channels, N-Type: CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.Calcium Channels, T-Type: A heterogenous group of transient or low voltage activated type CALCIUM CHANNELS. They are found in cardiac myocyte membranes, the sinoatrial node, Purkinje cells of the heart and the central nervous system.Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.Calcium Channel Agonists: Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.Ion Channel Gating: The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.Receptors, Cytoplasmic and Nuclear: Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.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.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.Inositol 1,4,5-Trisphosphate: Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin.Receptors, Interleukin-1: Cell surface receptors that are specific for INTERLEUKIN-1. Included under this heading are signaling receptors, non-signaling receptors and accessory proteins required for receptor signaling. Signaling from interleukin-1 receptors occurs via interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88.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.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 ProteinsProtein 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.

Multiple structural domains contribute to voltage-dependent inactivation of rat brain alpha(1E) calcium channels. (1/107)

We have investigated the molecular determinants that mediate the differences in voltage-dependent inactivation properties between rapidly inactivating (R-type) alpha(1E) and noninactivating (L-type) alpha(1C) calcium channels. When coexpressed in human embryonic kidney cells with ancillary beta(1b) and alpha(2)-delta subunits, the wild type channels exhibit dramatically different inactivation properties; the half-inactivation potential of alpha(1E) is 45 mV more negative than that observed with alpha(1C), and during a 150-ms test depolarization, alpha(1E) undergoes 65% inactivation compared with only about 15% for alpha(1C). To define the structural determinants that govern these intrinsic differences, we have created a series of chimeric calcium channel alpha(1) subunits that combine the major structural domains of the two wild type channels, and we investigated their voltage-dependent inactivation properties. Each of the four transmembrane domains significantly affected the half-inactivation potential, with domains II and III being most critical. In particular, substitution of alpha(1C) sequence in domains II or III with that of alpha(1E) resulted in 25-mV negative shifts in half-inactivation potential. Similarly, the differences in inactivation rate were predominantly governed by transmembrane domains II and III and to some extent by domain IV. Thus, voltage-dependent inactivation of alpha(1E) channels is a complex process that involves multiple structural domains and possibly a global conformational change in the channel protein.  (+info)

An R-type Ca(2+) current in neurohypophysial terminals preferentially regulates oxytocin secretion. (2/107)

Multiple types of voltage-dependent Ca(2+) channels are involved in the regulation of neurotransmitter release (Tsien et al., 1991; Dunlap et al., 1995). In the nerve terminals of the neurohypophysis, the roles of L-, N-, and P/Q-type Ca(2+) channels in neuropeptide release have been identified previously (Wang et al., 1997a). Although the L- and N-type Ca(2+) currents play equivalent roles in both vasopressin and oxytocin release, the P/Q-type Ca(2+) current only regulates vasopressin release. An oxytocin-release and Ca(2+) current component is resistant to the L-, N-, and P/Q-type Ca(2+) channel blockers but is inhibited by Ni(2+). A new polypeptide toxin, SNX-482, which is a specific alpha(1E)-type Ca(2+) channel blocker (Newcomb et al., 1998), was used to characterize the biophysical properties of this resistant Ca(2+) current component and its role in neuropeptide release. This resistant component was dose dependently inhibited by SNX-482, with an IC(50) of 4.1 nM. Furthermore, SNX-482 did not affect the other Ca(2+) current types in these CNS terminals. Like the N- and P/Q-type Ca(2+) currents, this SNX-482-sensitive transient Ca(2+) current is high-threshold activated and shows moderate steady-state inactivation. At the same concentrations, SNX-482 blocked the component of oxytocin, but not of vasopressin, release that was resistant to the other channel blockers, indicating a preferential role for this type of Ca(2+) current in oxytocin release from neurohypophysial terminals. Our results suggest that an alpha(1E) or "R"-type Ca(2+) channel exists in oxytocinergic nerve terminals and, thus, functions in controlling only oxytocin release from the rat neurohypophysis.  (+info)

Developmental changes in calcium channel types mediating central synaptic transmission. (3/107)

Multiple types of high-voltage-activated Ca(2+) channels trigger neurotransmitter release at the mammalian central synapse. Among them, the omega-conotoxin GVIA-sensitive N-type channels and the omega-Aga-IVA-sensitive P/Q-type channels mediate fast synaptic transmission. However, at most central synapses, it is not known whether the contributions of different Ca(2+) channel types to synaptic transmission remain stable throughout postnatal development. We have addressed this question by testing type-specific Ca(2+) channel blockers at developing central synapses. Our results indicate that N-type channels contribute to thalamic and cerebellar IPSCs only transiently during early postnatal period and P/Q-type channels predominantly mediate mature synaptic transmission, as we reported previously at the brainstem auditory synapse formed by the calyx of Held. In fact, Ca(2+) currents directly recorded from the auditory calyceal presynaptic terminal were identified as N-, P/Q-, and R-types at postnatal day 7 (P7) to P10 but became predominantly P/Q-type at P13. In contrast to thalamic and cerebellar IPSCs and brainstem auditory EPSCs, N-type Ca(2+) channels persistently contribute to cerebral cortical EPSCs and spinal IPSCs throughout postnatal months. Thus, in adult animals, synaptic transmission is predominantly mediated by P/Q-type channels at a subset of synapses and mediated synergistically by multiple types of Ca(2+) channels at other synapses.  (+info)

alpha(1E) subunits form the pore of three cerebellar R-type calcium channels with different pharmacological and permeation properties. (4/107)

R-type Ca(2+) channels cooperate with P/Q- and N-type channels to control neurotransmitter release at central synapses. The leading candidate as pore-forming subunit of R-type channels is the alpha(1E) subunit. However, R-type Ca(2+) currents with permeation and/or pharmacological properties different from those of recombinant Ca(2+) channels containing alpha(1E) subunits have been described, and therefore the molecular nature of R-type Ca(2+) channels remains not completely settled. Here, we show that the R-type Ca(2+) current of rat cerebellar granule cells consists of two components inhibited with different affinity by the alpha(1E) selective antagonist SNX482 (IC(50) values of 6 and 81 nM) and a third component resistant to SNX482. The SNX482-sensitive R-type current shows the unique permeation properties of recombinant alpha(1E) channels; it is larger with Ca(2+) than with Ba(2+) as charge carrier, and it is highly sensitive to Ni(2+) block and has a voltage-dependence of activation consistent with that of G2 channels with unitary conductance of 15 pS. On the other hand, the SNX482-resistant R-type current shows permeation properties similar to those of recombinant alpha(1A) and alpha(1B) channels; it is larger with Ba(2+) than with Ca(2+) as charge carrier(,) and it has a low sensitivity to Ni(2+) block and a voltage-dependence of activation consistent with that of G3 channels with unitary conductance of 20 pS. Gene-specific knock-down by antisense oligonucleotides demonstrates that the different cerebellar R-type channels are all encoded by the alpha(1E) gene, suggesting the existence of alpha(1E) isoforms with different pore properties.  (+info)

Calcium currents in hair cells isolated from semicircular canals of the frog. (5/107)

L-type and R-type Ca(2+) currents were detected in frog semicircular canal hair cells. The former was noninactivating and nifedipine-sensitive (5 microM); the latter, partially inactivated, was resistant to omega-conotoxin GVIA (5 microM), omega-conotoxin MVIIC (5 microM), and omega-agatoxin IVA (0.4 microM), but was sensitive to mibefradil (10 microM). Both currents were sensitive to Ni(2+) and Cd(2+) (>10 microM). In some cells the L-type current amplitude increased almost twofold upon repetitive stimulation, whereas the R-type current remained unaffected. Eventually, run-down occurred for both currents, but was prevented by the protease inhibitor calpastatin. The R-type current peak component ran down first, without changing its plateau, suggesting that two channel types generate the R-type current. This peak component appeared at -40 mV, reached a maximal value at -30 mV, and became undetectable for voltages > or =0 mV, suggestive of a novel transient current: its inactivation was indeed reversibly removed when Ba(2+) was the charge carrier. The L-type current and the R-type current plateau were appreciable at -60 mV and peaked at -20 mV: the former current did not reverse for voltages up to +60 mV, the latter reversed between +30 and +60 mV due to an outward Cs(+) current flowing through the same Ca(2+) channel. The physiological role of these currents on hair cell function is discussed.  (+info)

The spider toxin omega-Aga IIIA defines a high affinity site on neuronal high voltage-activated calcium channels. (6/107)

The spider toxin omega-agatoxin IIIA (omega-Aga-IIIA) is a potent inhibitor of high voltage-activated calcium currents in the mammalian brain. To establish the biochemical parameters governing its action, we radiolabeled the toxin and examined its binding to native and recombinant calcium channels. In experiments with purified rat synaptosomal membranes, both kinetic and equilibrium data demonstrate one-to-one binding of omega-Aga-IIIA to a single population of high affinity sites, with K(d) = approximately 9 pm and B(max) = approximately 1.4 pmol/mg protein. Partial inhibition of omega-Aga-IIIA binding by omega-conotoxins GVIA, MVIIA, and MVIIC identifies N and P/Q channels as components of this population. omega-Aga-IIIA binds to recombinant alpha(1B) and alpha(1E) calcium channels with a similar high affinity (K(d) = approximately 5-9 pm) in apparent one-to-one fashion. Results from recombinant alpha(1B) binding experiments demonstrate virtually identical B(max) values for omega-Aga-IIIA and omega-conotoxin MVIIA, providing further evidence for a one-to-one stoichiometry of agatoxin binding to calcium channels. The combined evidence suggests that omega-Aga-IIIA defines a unique, high affinity binding site on N-, P/Q-, and R-type calcium channels.  (+info)

CaV2.2 and CaV2.3 (N- and R-type) Ca2+ channels in depolarization-evoked entry of Ca2+ into mouse sperm. (7/107)

As sperm prepare for fertilization, surface Ca(2+) channels must open to initiate required, Ca(2+)-mediated events. However, the molecular identity and functional properties of sperm Ca(2+) channels remain uncertain. Here, we use rapid local perfusion and single-cell photometry to examine the kinetics of calcium responses of mouse sperm to depolarizing stimuli. The linear rise of intracellular [Ca(2+)] evoked by approximately 10-s applications of an alkaline high [K(+)] medium directly reports activity of voltage-gated Ca(2+) channels. Little response occurs if external Ca(2+) is removed or if external or internal pH is elevated without depolarization. Responses are inhibited 30-40% by 30-100 micrometer Ni(2+) and more completely by 100-300 micrometer Cd(2+). They resist the dihydropyridines nitrendipine and PN200-110, but 1-10 micrometer mibefradil inhibits reversibly. They also resist the venom toxins calciseptine, omega-conotoxin MVIIC, and kurtoxin, but omega-conotoxin GVIA (5 micrometer) inhibits approximately 50%. GVIA also partially blocks transient, low voltage activated Ca(2+) currents of patch-clamped spermatids. Differential sensitivity of sperm responses to Ni(2+) and Cd(2+) and partial blockade by GVIA indicate that depolarization opens at least two types of voltage-gated Ca(2+) channels in epididymal sperm examined prior to capacitation. Involvement of a previously undetected Ca(V)2.2 (N-type) channel, suggested by the action of GVIA, is substantiated by immunodetection of Ca(2+) channel alpha(1B) subunits in sperm and sperm extracts. Resistance to dihydropyridines, calciseptine, MVIIC, and kurtoxin indicates that Ca(V)1, Ca(V)2.1, and Ca(V)3 (L-, P/Q-, and T-type) channels contribute little to this evoked response. Partial sensitivity to 1 micrometer mibefradil and an enhanced sensitivity of the GVIA-resistant component of response to Ni(2+) suggest participation of a Ca(V)2.3 (R-type) channel specified by previously found alpha(1E) subunits. Our examination of depolarization-evoked Ca(2+) entry indicates that mature sperm possess a larger palette of voltage-gated Ca(2+) channels than previously thought. Such diversity may permit specific responses to multiple cues encountered on the path to fertilization.  (+info)

Altered pain responses in mice lacking alpha 1E subunit of the voltage-dependent Ca2+ channel. (8/107)

alpha(1) subunit of the voltage-dependent Ca(2+) channel is essential for channel function and determines the functional specificity of various channel types. alpha(1E) subunit was originally identified as a neuron-specific one, but the physiological function of the Ca(2+) channel containing this subunit (alpha(1E) Ca(2+) channel) was not clear compared with other types of Ca(2+) channels because of the limited availability of specific blockers. To clarify the physiological roles of the alpha(1E) Ca(2+) channel, we have generated alpha(1E) mutant (alpha(1E)-/-) mice by gene targeting. The lacZ gene was inserted in-frame and used as a marker for alpha(1E) subunit expression. alpha(1E)-/- mice showed reduced spontaneous locomotor activities and signs of timidness, but other general behaviors were apparently normal. As involvement of alpha(1E) in pain transmission was suggested by localization analyses with 5-bromo-4-chloro-3-indolyl beta-d-galactopyranoside staining, we conducted several pain-related behavioral tests using the mutant mice. Although alpha(1E)+/- and alpha(1E)-/- mice exhibited normal pain behaviors against acute mechanical, thermal, and chemical stimuli, they both showed reduced responses to somatic inflammatory pain. alpha(1E)+/- mice showed reduced response to visceral inflammatory pain, whereas alpha(1E)-/- mice showed apparently normal response compared with that of wild-type mice. Furthermore, alpha(1E)-/- mice that had been presensitized with a visceral noxious conditioning stimulus showed increased responses to a somatic inflammatory pain, in marked contrast with the wild-type mice in which long-lasting effects of descending antinociceptive pathway were predominant. These results suggest that the alpha(1E) Ca(2 +) channel controls pain behaviors by both spinal and supraspinal mechanisms.  (+info)

*R-type calcium channel

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 ...

*Q-type calcium channel

The Q-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α1 subunit is the ... They are poorly understood, but like R-type calcium channels, they appear to be present in cerebellar granule cells. They have ... Q-Type Calcium Channel at the US National Library of Medicine Medical Subject Headings (MeSH). ... one that determines most of the channel's properties. ...

*P-type calcium channel

The P-type calcium channel is a type of voltage-dependent calcium channel. Similar to many other high-voltage-gated calcium ... P-type calcium channels play a similar role to the N-type calcium channel in neurotransmitter release at the presynaptic ... There are many different types of calcium channels, so to prove that the P/Q type calcium channels are directly involved, a P/Q ... corresponds to what is functionally defined as the P-type and Q-type isoforms. P-type and Q-type calcium channels are closely ...

*T-type calcium channel

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 ...

*N-type calcium channel

... which is also similar to another type of calcium channels, known as P-type calcium channels. N-type calcium channels are ... N-type calcium channels are voltage gated calcium channels that are distributed throughout the entire body. These channels are ... The inhibition of this channel by calcium channel blockers can lead to renal microcirculation. N-type calcium channels have ... N-type calcium channels have known functions in the kidney, and heart. There are many known N-type calcium channel blockers, ...

*L-type calcium channel

The L-type calcium channel (also known as the dihydropyridine channel, or DHP channel) is part of the high-voltage activated ... This channel has four subunits (Cav1.1, Cav1.2, Cav1.3, Cav1.4). L-type calcium channels are responsible for the excitation- ... In cardiac myocytes, the L-type calcium channel passes inward Ca2+ current and triggers calcium release from the sarcoplasmic ... Rossier, Michel F. (2016). "T-Type Calcium Channel: A Privileged Gate for Calcium Entry and Control of Adrenal Steroidogenesis ...

*Calcium channel

the receptor-operated calcium channels (in vasoconstriction) P2X receptors L-type calcium channel blockers are used to treat ... T-type calcium channel blockers are used to treat epilepsy. Increased calcium conductance in the neurons leads to increased ... A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous as voltage- ... "calcium channel" at Dorland's Medical Dictionary Striggow F, Ehrlich BE (August 1996). "Ligand-gated calcium channels inside ...

*Calcium channel blocker

N-type, L-type, and T-type voltage-dependent calcium channels are present in the zona glomerulosa of the human adrenal, and ... Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are several medications that disrupt the ... may increase or enhance the effects of calcium channel blockade. N-type calcium channels are found in neurons and are involved ... Calcium channel blockers prevent or reduce the opening of these channels and thereby reduce these effects. Several types of ...

*Calcium-induced calcium release

When an action potential depolarizes the cell membrane, voltage-gated Ca2+ channels (e.g., L-type calcium channels) are ... Calcium-induced calcium release (CICR) describes a biological process whereby calcium is able to activate calcium release from ... Fabiato, A. (1983). "Calcium-induced calcium release from the cardiac sarcoplasmic reticulum". American Journal of Physiology. ... Endo, M (1977). "Calcium release from the sarcoplasmic reticulum". Physiological Reviews. 57 (1): 71-108. PMID 13441. ...

*Cav1.2

"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 ...

*Childhood absence epilepsy

"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 ...

*CACNA1B

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 ...

*CACNG3

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 ...

*CACNG1

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 ...

*CACNG4

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: ...

*CACNG2

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 ...

*Low-threshold spikes

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. ...

*BRL-32872

Structural model for phenylalkylamine binding to L-type calcium channels. The Journal of Biological Chemistry, 284(41), 28332- ... The drug targets L-type Ca+2 channels, and decreases conduction in cells where Ca+2 is required for action potential upstroke ( ... 1995). Electrophysiological effect of BRL-32872, a novel antiarrhythmic agent with potassium and calcium channel blocking ... BRL-32872's class III activity is directed towards the human ether-a-go-go-related gene (hERG) K+ channel. hERG channels are ...

*Calcium channel opener

A calcium channel opener is a type of drug which facilitates ion transmission through calcium channels. An example is Bay K8644 ... mucolipin TRP channels (TRPMLs) and purinergic receptors of the P2X channel type. Calcium channel blocker Schramm M, Thomas G, ... Calcium permeable ion channels in lysosomal membranes that may be activated by a luminal pH increase include two pore channels ... which is an analogue of nifedipine that specifically and directly activates L-type voltage-dependent calcium channels. In ...

*Neuromuscular junction

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+ ...

*Timothy syndrome

... 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 ...

*Efonidipine

... 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 ...

*Bay K8644

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: ...

*Ical

... an ionic current through the L-type calcium channel. ...

*AH-1058

... 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 ...

*Metabolism

For example, muscle contraction depends upon the movement of calcium, sodium and potassium through ion channels in the cell ... Reaction centers are classed into two types depending on the type of photosynthetic pigment present, with most photosynthetic ... Three types of photosynthesis occur in plants, C3 carbon fixation, C4 carbon fixation and CAM photosynthesis. These differ by ... Hundreds of separate types of dehydrogenases remove electrons from their substrates and reduce NAD+ into NADH. This reduced ...
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 ...
... calcium channel, voltage-dependent, R type, alpha 1E subunit Identifiers Symbol CACNA1E Alt. Symbols CACNL1A6 Entrez 777 HUGO 1392 OMIM
Ulises Meza, Ashish Thapliyal, Roger A Bannister, Brett A Adams. Mol. Pharmacol., 2007 Jan , 71, 284-93. Neurokinin (NK) 1 receptors and CaV2.3 calcium channels are both expressed in nociceptive neurons, and mice lacking either protein display altered responses to noxious stimuli. Here, we examined modulation of CaV2.3 through NK1 receptors expressed in human embryonic kidney 293 cells. We find that NK1 receptors generate complex modulation of CaV2.3. In particular, weak activation of these receptors evokes mainly stimulation of CaV2.3, whereas strong receptor activation elicits profound inhibition that overlaps with channel stimulation. Unlike R-type channels encoded by CaV2.3, L-type (CaV1.3), N-type (CaV2.2), and P/Q-type (CaV2.1) channels are inhibited, but not stimulated, through NK1 receptors. Pharmacological experiments show that protein kinase C (PKC) mediates stimulation of CaV2.3 through NK1 receptors. The signaling mechanisms underlying inhibition were explored by expressing proteins ...
I used save states to practice for most games if they were available in MAME or other emulators. For example, R-Type took me three days to 1CC with save state practice. At my kuso level of skill I generally expect most games will take four days of 2 hours+ per day of save state practice to memorize. That is about a 5 in difficulty. Though various factors may also affect the final difficulty ratings (R-Type basically requiring a one life clear bumps it up a couple points). 1s were generally blind 1CCs. DDP DOJ, the only 10 in my ratings so far, took me 60 hours with focused practice. All final runs were done clean without save states. Much like learning an instrument, I firmly believe in trying to use the most efficient practice possible until you are ready to perform the real thing. Not all games have save state practice available like X-Box 360 only ports and that may affect difficulty ratings as well. I also generally used auto fire when available. I understand there will be some ...
Patients are randomized to receive SNX-111 or placebo (AS PER AMENDMENT 1/22/98: with randomization weighted 2:1 in favor of SNX-111) via external pump and an intrathecal catheter (thin tube inserted into the spinal canal). (AS PER AMENDMENT 1/22/98: the dose is increased every 24 hours, in the absence of onset of analgesia or adverse events. After 2-5 days, patients who respond to their medication continue treatment at home for 5-8 days. Patients who do not respond will be switched to the other regimen (i.e., placebo to SNX-111, or SNX-111 to placebo). After 10 days, responding patients are unblinded and asked to enroll in the long-term, open-label extension protocol. Patients remain on a fixed dose at the therapeutic level found in the previous study. The dose may be increased or decreased at the discretion of the investigator. Patients may continue therapy on a long-term basis until the drug is approved ...
Patients are randomized to receive SNX-111 or placebo (AS PER AMENDMENT 1/22/98: with randomization weighted 2:1 in favor of SNX-111) via external pump and an intrathecal catheter (thin tube inserted into the spinal canal). (AS PER AMENDMENT 1/22/98: the dose is increased every 24 hours, in the absence of onset of analgesia or adverse events. After 2-5 days, patients who respond to their medication continue treatment at home for 5-8 days. Patients who do not respond will be switched to the other regimen (i.e., placebo to SNX-111, or SNX-111 to placebo). After 10 days, responding patients are unblinded and asked to enroll in the long-term, open-label extension protocol. Patients remain on a fixed dose at the therapeutic level found in the previous study. The dose may be increased or decreased at the discretion of the investigator. Patients may continue therapy on a long-term basis until the drug is approved ...
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Lu Yihe, Y Timofeeva 2016 Response functions for electrically coupled neuronal network: a method of local point matching and its applications Biological Cybernetics, pp 1-17, doi: 10.1007/s00422-016-0681-y. Y Timofeeva, K Volynski 2015 Calmodulin as a major calcium buffer shaping vesicular release and short-term synaptic plasticity: facilitation through buffer dislocation Frontiers in Cellular Neuroscience 9:239, doi: 10.3389/fncel.2015.00239. Y S Ermolyuk, F G Alder, R Surges, I Y Pavlov, Y Timofeeva, D M Kullmann, K E Volynski 2013 Differential triggering of spontaneous glutamate release by P/Q-, N- and R-type Ca2+ channels, Nature Neuroscience, 16, 1754-1763, doi:10.1038/nn.3563. Y Timofeeva, S Coombes Network response of gap junction coupled dendrites, in "Dendritic Computations through Morphology and Connectivity", Springer, 2013. Y Timofeeva Complexity and Chaos in Dynamical Systems, in "Masters of Complexity Science", the London Mathematical Society Lecture Note Series, 2013. Y Timofeeva, ...
Long cycling life is one prerequisite for the commercial application of hydrogen storage materials. The cycling stability of a promising Mg + Mg2Ni + YH2 hydrogen storage nanocomposite made by hydrogen-induced decomposition of the 18R-type long period stacking ordered (LPSO) structure is investigated. At 300
Voltage-gated sodium channels, which initiate action potentials in mammalian brain neurons, are modulated functionally by cAMP-dependent protein kinase A (PKA), resulting in reduced sodium current amplitude. Comparing brain and muscle sodium channels, we show that only the brain channel is modulated by PKA. The brain sodium channel I-II linker is both necessary and sufficient for PKA modulation, as shown by exchanging the I-II linker regions of the two channels. PKA consensus sites in the brain channel I-II linker were eliminated by deletion and site-specific mutagenesis. The mutant channels demonstrated decreased levels of phosphorylation when metabolically labeled in oocytes with [gamma-32P]-ATP, and they did not respond with a reduction in current magnitude after PKA induction. Modulation of the brain channel by PKA phosphorylation was mimicked by adding fixed negative charges at the PKA consensus sites, suggesting that the decrease in current was a direct result of the negative charge at one ...
Since May 2013, 17 pts were enrolled. No dose-limiting toxicities (DLTs) were reported in the first cohort (SNX-5422 50 mg/m2 + E), but DLTs (diarrhoea) were reported by 2 pts in the second cohort (SNX-5422 75 mg/m2 + E). Adverse events possibly related to the combination in ≥ 4 of 17 pts in were diarrhoea, nausea, fatigue, dry eyes, paronychia, and rash, all graded 1 or 2; except for 2 cases of grade 3 diarrhoea. No cardiovascular, renal or hepatic toxicities have been observed. 1 Pt reported mild, reversible nictalopia at the DLT level of SNX-5422 75 mg/m2 + E. Pts received a median of two cycles (range 1-6), and 3 remain on study. No partial responses have been seen in 15 evaluable pts; 1 ongoing pt had an 18% decrease from baseline in target lesions in Cycle 4. Stable disease was the best response in 4 pts at 8 wks, 3 pts at 16 weeks and 1 pt at 24 weeks. ...
Since May 2013, 17 pts were enrolled. No dose-limiting toxicities (DLTs) were reported in the first cohort (SNX-5422 50 mg/m2 + E), but DLTs (diarrhoea) were reported by 2 pts in the second cohort (SNX-5422 75 mg/m2 + E). Adverse events possibly related to the combination in ≥ 4 of 17 pts in were diarrhoea, nausea, fatigue, dry eyes, paronychia, and rash, all graded 1 or 2; except for 2 cases of grade 3 diarrhoea. No cardiovascular, renal or hepatic toxicities have been observed. 1 Pt reported mild, reversible nictalopia at the DLT level of SNX-5422 75 mg/m2 + E. Pts received a median of two cycles (range 1-6), and 3 remain on study. No partial responses have been seen in 15 evaluable pts; 1 ongoing pt had an 18% decrease from baseline in target lesions in Cycle 4. Stable disease was the best response in 4 pts at 8 wks, 3 pts at 16 weeks and 1 pt at 24 weeks. ...
September 24, 2012 DuPont Nutrition & Health has announced a strategic collaboration with AvidBiotics Corp. to develop novel bactericidal protein technologies. Through this agreement, which includes a DuPont Ventures equity investment, DuPont will gain exclusive, worldwide rights to the technologies for food and food protection applications.. AvidBiotics develops novel, non-antibody proteins targeted against bacteria, viral infections, and cancer. AvidBiotics antibacterial technology is based on R-type bacteriocins (proteins with bactericidal activity). These proteins recognize target bacteria by binding to specific receptors on the bacterial surface, then disrupting the cell envelope to kill the organism promptly. In theory, R-type bacteriocins can be developed against any pathogenic bacteria or spoilage organism of interest.. "Ensuring the safety, freshness, and quality of products throughout shelf life is at the top of the food industry agenda, and we are excited by the prospect of ...

R-type calcium channel - WikipediaR-type calcium channel - Wikipedia

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 ...
more infohttps://en.wikipedia.org/wiki/R-type_calcium_channel

Selective N-Type Calcium Channel Antagonist Omega Conotoxin MVIIA Is Neuroprotective Against Hypoxic Neurodegeneration in...Selective N-Type Calcium Channel Antagonist Omega Conotoxin MVIIA Is Neuroprotective Against Hypoxic Neurodegeneration in...

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 ...
more infohttp://stroke.ahajournals.org/content/27/11/2124

IDEALS @ Illinois: Calcium Influx via the T-Type Calcium Channel Plays a Permissive Role in Proliferation of Mouse Embryonic Hl...IDEALS @ Illinois: Calcium Influx via the T-Type Calcium Channel Plays a Permissive Role in Proliferation of Mouse Embryonic Hl...

... 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 ...
more infohttps://www.ideals.illinois.edu/handle/2142/87230

Synthesis and biological evaluation of 1-(2-hydroxy-3-phenyloxypropyl) piperazine derivatives as T-type calcium channel...Synthesis and biological evaluation of 1-(2-hydroxy-3-phenyloxypropyl) piperazine derivatives as T-type calcium channel...

... 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 ...
more infohttps://koreauniv.pure.elsevier.com/en/publications/synthesis-and-biological-evaluation-of-1-2-hydroxy-3-phenyloxypro

Amlodipine Besylate ManufacturersAmlodipine Besylate Manufacturers

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 ...
more infohttp://cadilapharma.com/pharma_api/amlodipine-besylate-manufacturers/

Nimodipine Order Online - Mexico Pharmacy Nimodipine - Nimodipine 100mg Price WalmartNimodipine Order Online - Mexico Pharmacy Nimodipine - Nimodipine 100mg Price Walmart

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 ...
more infohttp://nimodipine.vuli.info

Targetable T-type Calcium Channels Drive Glioblastoma | Cancer ResearchTargetable T-type Calcium Channels Drive Glioblastoma | Cancer Research

... 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, ...
more infohttp://cancerres.aacrjournals.org/content/77/13/3479

T-type calcium channels in burst-firing, network synchrony, and epilepsy.  - PubMed - NCBIT-type calcium channels in burst-firing, network synchrony, and epilepsy. - PubMed - NCBI

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 ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/22885138?dopt=Abstract

Calmodulin supports both inactivation and facilitation of L-type calcium channels.  - PubMed - NCBICalmodulin supports both inactivation and facilitation of L-type calcium channels. - PubMed - NCBI

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 ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/10335846?dopt=Abstract

Voltage-dependent L-type calcium channel - DrugBankVoltage-dependent L-type calcium channel - DrugBank

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 ...
more infohttps://www.drugbank.ca/bio_entities/BE0008715

Voltage-dependent calcium channel, L-type, alpha-1S subunit (IPR005450) | InterPro | EMBL-EBIVoltage-dependent calcium channel, L-type, alpha-1S subunit (IPR005450) | InterPro | EMBL-EBI

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 ...
more infohttps://www.ebi.ac.uk/interpro/entry/IPR005450

Marine Drugs | Free Full-Text | Inhibition of N-Type Calcium Channels by Fluorophenoxyanilide DerivativesMarine Drugs | Free Full-Text | Inhibition of N-Type Calcium Channels by Fluorophenoxyanilide Derivatives

... 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. ...
more infohttp://www.mdpi.com/1660-3397/13/4/2030

Lateral Mobility of Presynaptic L-Type Calcium Channels at Photoreceptor Ribbon Synapses | Journal of NeuroscienceLateral Mobility of Presynaptic L-Type Calcium Channels at Photoreceptor Ribbon Synapses | Journal of Neuroscience

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 ...
more infohttp://www.jneurosci.org/content/31/12/4397

Voltage-dependent L-type calcium channel subunit alpha-1D - DrugBankVoltage-dependent L-type calcium channel subunit alpha-1D - DrugBank

Voltage-dependent L-type calcium channel subunit alpha-1D. Details. Name. Voltage-dependent L-type calcium channel subunit ... Voltage-dependent L-type calcium channel subunit alpha-1D. Q01668. Details. Drug Relations. Drug Relations. DrugBank ID. Name. ...
more infohttps://www.drugbank.ca/biodb/bio_entities/BE0002359

Selective T-Type Calcium Channel Blockade Alleviates Hyperalgesia in ob/ob Mice | DiabetesSelective T-Type Calcium Channel Blockade Alleviates Hyperalgesia in ob/ob Mice | Diabetes

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; ...
more infohttp://diabetes.diabetesjournals.org/content/58/11/2656.full

N-Type Calcium Channels
      - N-Type Calcium Channel
     Summary Report | CureHunterN-Type Calcium Channels - N-Type Calcium Channel Summary Report | CureHunter

CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their ... Channels, N-Type Calcium; Channels, Neural-Type Calcium; N Type Calcium Channel; N Type Calcium Channels; N Type VDCC; N Type ... N-Type Calcium Channel; Calcium Channels, N-Type; N-Type VDCC; N-Type Voltage-Dependent Calcium Channels; Calcium Channel, N- ... Type; Calcium Channels, N Type; Calcium Channels, Neural-Type; Channel, N-Type Calcium; ...
more infohttp://www.curehunter.com/public/keywordSummaryD020864-N-Type-Calcium-Channels-N-Type-Calcium-Channel.do

Q-type calcium channel - WikipediaQ-type calcium channel - Wikipedia

The Q-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α1 subunit is the ... They are poorly understood, but like R-type calcium channels, they appear to be present in cerebellar granule cells. They have ... Q-Type Calcium Channel at the US National Library of Medicine Medical Subject Headings (MeSH). ... one that determines most of the channels properties. ...
more infohttps://en.wikipedia.org/wiki/Q-type_calcium_channel

Voltage-Dependent T-Type Calcium Channel Blockers -Pipeline Insight, 2019Voltage-Dependent T-Type Calcium Channel Blockers -Pipeline Insight, 2019

"Voltage-Dependent T-Type Calcium Channel Blockers. The report assesses the active Voltage-Dependent T-Type Calcium Channel ... "Voltage-Dependent T-Type Calcium Channel Blockers. • Features the Voltage-Dependent T-Type Calcium Channel Blockers pipeline ... "Voltage-Dependent T-Type Calcium Channel Blockers - Pipeline Insight, 2019" offers comprehensive insights of the pipeline ( ... Voltage-Dependent T-Type Calcium Channel Blockers -Pipeline Insight, 2019. *January 2019 • ...
more infohttps://www.reportbuyer.com/product/5129791/voltage-dependent-t-type-calcium-channel-blockers-pipeline-insight-2019.html

Abstract 16089: Functional Coupling of SK Channels and L-type Calcium Channels in Cardiomyocytes | CirculationAbstract 16089: Functional Coupling of SK Channels and L-type Calcium Channels in Cardiomyocytes | Circulation

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 ...
more infohttp://circ.ahajournals.org/content/132/Suppl_3/A16089

Depolarization-stimulated cholecystokinin secretion is mediated by L-type calcium channels in STC-1 cells | RTIDepolarization-stimulated cholecystokinin secretion is mediated by L-type calcium channels in STC-1 cells | RTI

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 ...
more infohttps://www.rti.org/publication/depolarization-stimulated-cholecystokinin-secretion-mediated-l-type-calcium-channels-stc

Molecular Mechanisms of Lipoic Acid Modulation of T-Type Calcium Channels in Pain Pathway | Journal of NeuroscienceMolecular Mechanisms of Lipoic Acid Modulation of T-Type Calcium Channels in Pain Pathway | Journal of Neuroscience

2007a) Reducing agents sensitize C-type nociceptors by relieving high-affinity zinc inhibition of T-type calcium channels. J ... 2005) Silencing of the CaV3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception. EMBO J ... Molecular Mechanisms of Lipoic Acid Modulation of T-Type Calcium Channels in Pain Pathway. Woo Yong Lee, Peihan Orestes, ... 2001b) Cav3.2 channel is a molecular substrate for inhibition of T-type calcium currents in rat sensory neurons by nitrous ...
more infohttp://www.jneurosci.org/content/29/30/9500

calcium channel, voltage-dependent, L type, alpha 1S subunit ELISA Kits | Biocompare.comcalcium channel, voltage-dependent, L type, alpha 1S subunit ELISA Kits | Biocompare.com

L type, alpha 1S subunit ELISA Kits from leading suppliers on Biocompare. View specifications, prices, citations, reviews, and ... calcium channel, voltage-dependent, L type, alpha 1S subunit ELISA Kits. Clear ... calcium channel, voltage-dependent, L type, alpha 1S subunit ELISA Kits. The ELISA (enzyme-linked immunosorbent assay) is a ... Mouse Calcium Channel, Voltage Dependent, L-Type, Alpha 1S Subunit (CACNa1S) ELISA Kit ...
more infohttps://www.biocompare.com/pfu/110627/soids/2-321525/Assay_Kit/ELISA_calcium_channel_voltage-dependent_L_type_alpha_1S_subunit

Estradiol receptor antagonist reduces ventricular arrhythmia via L-type calcium channels in chronic heart failure.Estradiol receptor antagonist reduces ventricular arrhythmia via L-type calcium channels in chronic heart failure.

... Minerva ... Estradiol receptor antagonist reduces ventricular arrhythmia via L-type calcium channels in chronic heart failure.. *. ... Estradiol receptor antagonist reduces ventricular arrhythmia via L-type calcium channels in chronic heart failure. Minerva ... Exendin-4 Reduces Ventricular Arrhythmia Activity and Calcium Sparks-Mediated Sarcoplasmic Reticulum Ca Leak in Rats with Heart ...
more infohttps://medworm.com/759935708/estradiol-receptor-antagonist-reduces-ventricular-arrhythmia-via-l-type-calcium-channels-in-chronic-/

Reversal of Neuropathic Pain in Diabetes by Targeting Glycosylation of Cav3.2 T-Type Calcium Channels | DiabetesReversal of Neuropathic Pain in Diabetes by Targeting Glycosylation of Cav3.2 T-Type Calcium Channels | Diabetes

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 ...
more infohttp://diabetes.diabetesjournals.org/content/62/11/3828.supplemental

Deletion of T-type calcium channels Cav3.1 or Cav3.2 attenuates endothelial dysfunction in aging mice | SpringerLinkDeletion of T-type calcium channels Cav3.1 or Cav3.2 attenuates endothelial dysfunction in aging mice | SpringerLink

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. ...
more infohttps://link.springer.com/article/10.1007%2Fs00424-017-2068-x
  • To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 2-hydroxy-3-phenoxypropyl piperazine derivatives were synthesized and evaluated for in vitro activities. (elsevier.com)
  • Compound 6m and 6q showed high selectivity over hERG channel (IC 50 ratio of hERG/α 1G 6m = 8.5, 6q = 18.38) and they were subjected to measure pharmacokinetics profiles. (elsevier.com)
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