Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Calcium Channels, L-Type: Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.Calcium Channels, N-Type: CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.Calcium Channels, T-Type: A heterogenous group of transient or low voltage activated type CALCIUM CHANNELS. They are found in cardiac myocyte membranes, the sinoatrial node, Purkinje cells of the heart and the central nervous system.Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.Calcium Channel Agonists: Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.Ion Channel Gating: The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.Potassium Channels, Inwardly Rectifying: Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.Calcium Channels, P-Type: CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.Calcium Channels, Q-Type: CALCIUM CHANNELS located in the neurons of the brain.Dihydropyridines: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.Calcium Channels, R-Type: CALCIUM CHANNELS located in the neurons of the brain. They are inhibited by the marine snail toxin, omega conotoxin MVIIC.Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.Potassium Channel Blockers: A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.Chloride Channels: Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.omega-Conotoxin GVIA: A neurotoxic peptide, which is a cleavage product (VIa) of the omega-Conotoxin precursor protein contained in venom from the marine snail, CONUS geographus. It is an antagonist of CALCIUM CHANNELS, N-TYPE.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Calcium, Dietary: Calcium compounds used as food supplements or in food to supply the body with calcium. Dietary calcium is needed during growth for bone development and for maintenance of skeletal integrity later in life to prevent osteoporosis.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).omega-Conotoxins: A family of structurally related neurotoxic peptides from mollusk venom that inhibit voltage-activated entry of calcium into the presynaptic membrane. They selectively inhibit N-, P-, and Q-type calcium channels.Potassium Channels, Voltage-Gated: Potassium channel whose permeability to ions is extremely sensitive to the transmembrane potential difference. The opening of these channels is induced by the membrane depolarization of the ACTION POTENTIAL.Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.KATP Channels: Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent.Isradipine: A potent antagonist of CALCIUM CHANNELS that is highly selective for VASCULAR SMOOTH MUSCLE. It is effective in the treatment of chronic stable angina pectoris, hypertension, and congestive cardiac failure.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Potassium Channels, Calcium-Activated: Potassium channels whose activation is dependent on intracellular calcium concentrations.Nitrendipine: A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive.Mibefradil: A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE.Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.Sodium Channel Blockers: A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous.Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.omega-Agatoxin IVA: A neuropeptide toxin from the venom of the funnel web spider, Agelenopsis aperta. It inhibits CALCIUM CHANNELS, P-TYPE by altering the voltage-dependent gating so that very large depolarizations are needed for channel opening. It also inhibits CALCIUM CHANNELS, Q-TYPE.TRPC Cation Channels: A subgroup of TRP cation channels that contain 3-4 ANKYRIN REPEAT DOMAINS and a conserved C-terminal domain. Members are highly expressed in the CENTRAL NERVOUS SYSTEM. Selectivity for calcium over sodium ranges from 0.5 to 10.Shaker Superfamily of Potassium Channels: Voltage-gated potassium channels whose primary subunits contain six transmembrane segments and form tetramers to create a pore with a voltage sensor. They are related to their founding member, shaker protein, Drosophila.Kinetics: The rate dynamics in chemical or physical systems.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Large-Conductance Calcium-Activated Potassium Channels: A major class of calcium activated potassium channels whose members are voltage-dependent. MaxiK channels are activated by either membrane depolarization or an increase in intracellular Ca(2+). They are key regulators of calcium and electrical signaling in a variety of tissues.Potassium: An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.Calcium Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement.Cyclic Nucleotide-Gated Cation Channels: A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore-loop cation channels. They are expressed in OLFACTORY NERVE cilia and in PHOTORECEPTOR CELLS and some PLANTS.Oocytes: Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Calcium Chloride: A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.TRPV Cation Channels: A subgroup of TRP cation channels named after vanilloid receptor. They are very sensitive to TEMPERATURE and hot spicy food and CAPSAICIN. They have the TRP domain and ANKYRIN repeats. Selectivity for CALCIUM over SODIUM ranges from 3 to 100 fold.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Nicardipine: A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents.Xenopus laevis: The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Ryanodine Receptor Calcium Release Channel: A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.TRPM Cation Channels: A subgroup of TRP cation channels named after melastatin protein. They have the TRP domain but lack ANKYRIN repeats. Enzyme domains in the C-terminus leads to them being called chanzymes.Acid Sensing Ion Channels: A family of proton-gated sodium channels that are primarily expressed in neuronal tissue. They are AMILORIDE-sensitive and are implicated in the signaling of a variety of neurological stimuli, most notably that of pain in response to acidic conditions.Spider Venoms: Venoms of arthropods of the order Araneida of the ARACHNIDA. The venoms usually contain several protein fractions, including ENZYMES, hemolytic, neurolytic, and other TOXINS, BIOLOGICAL.Calcium Phosphates: Calcium salts of phosphoric acid. These compounds are frequently used as calcium supplements.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Epithelial Sodium Channels: Sodium channels found on salt-reabsorbing EPITHELIAL CELLS that line the distal NEPHRON; the distal COLON; SALIVARY DUCTS; SWEAT GLANDS; and the LUNG. They are AMILORIDE-sensitive and play a critical role in the control of sodium balance, BLOOD VOLUME, and BLOOD PRESSURE.Kv1.3 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.Ether-A-Go-Go Potassium Channels: A family of voltage-gated potassium channels that are characterized by long N-terminal and C-terminal intracellular tails. They are named from the Drosophila protein whose mutation causes abnormal leg shaking under ether anesthesia. Their activation kinetics are dependent on extracellular MAGNESIUM and PROTON concentration.Calcium Isotopes: Stable calcium atoms that have the same atomic number as the element calcium, but differ in atomic weight. Ca-42-44, 46, and 48 are stable calcium isotopes.Kv1.2 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.Kv1.1 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.Calcium Radioisotopes: Unstable isotopes of calcium that decay or disintegrate emitting radiation. Ca atoms with atomic weights 39, 41, 45, 47, 49, and 50 are radioactive calcium isotopes.Protein Subunits: Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.Amlodipine: A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of ANGINA PECTORIS and HYPERTENSION.Kv1.5 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that conducts a delayed rectifier current. It contributes to ACTION POTENTIAL repolarization of MYOCYTES in HEART ATRIA.Agatoxins: A class of polyamine and peptide toxins which are isolated from the venom of spiders such as Agelenopsis aperta.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Small-Conductance Calcium-Activated Potassium Channels: A major class of calcium-activated potassium channels that are found primarily in excitable CELLS. They play important roles in the transmission of ACTION POTENTIALS and generate a long-lasting hyperpolarization known as the slow afterhyperpolarization.Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active, passive or facilitated. Ions may travel by themselves (uniport), or as a group of two or more ions in the same (symport) or opposite (antiport) directions.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Mollusk Venoms: Venoms from mollusks, including CONUS and OCTOPUS species. The venoms contain proteins, enzymes, choline derivatives, slow-reacting substances, and several characterized polypeptide toxins that affect the nervous system. Mollusk venoms include cephalotoxin, venerupin, maculotoxin, surugatoxin, conotoxins, and murexine.Transient Receptor Potential Channels: A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN repeats are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES.KCNQ Potassium Channels: A family of delayed rectifier voltage-gated potassium channels that share homology with their founding member, KCNQ1 PROTEIN. KCNQ potassium channels have been implicated in a variety of diseases including LONG QT SYNDROME; DEAFNESS; and EPILEPSY.Shab Potassium Channels: A subfamily of shaker potassium channels that shares homology with its founding member, Shab protein, Drosophila. They regulate delayed rectifier currents in the NERVOUS SYSTEM of DROSOPHILA and in the SKELETAL MUSCLE and HEART of VERTEBRATES.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.KCNQ1 Potassium Channel: A voltage-gated potassium channel that is expressed primarily in the HEART.Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Shaw Potassium Channels: A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.Kv1.4 Potassium Channel: A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.Tetrodotoxin: An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Calcium Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Chelating Agents: Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS.Gallopamil: Coronary vasodilator that is an analog of iproveratril (VERAPAMIL) with one more methoxy group on the benzene ring.G Protein-Coupled Inwardly-Rectifying Potassium Channels: A family of inwardly-rectifying potassium channels that are activated by PERTUSSIS TOXIN sensitive G-PROTEIN-COUPLED RECEPTORS. GIRK potassium channels are primarily activated by the complex of GTP-BINDING PROTEIN BETA SUBUNITS and GTP-BINDING PROTEIN GAMMA SUBUNITS.Calcium Gluconate: The calcium salt of gluconic acid. The compound has a variety of uses, including its use as a calcium replenisher in hypocalcemic states.Shal Potassium Channels: A shaker subfamily of potassium channels that participate in transient outward potassium currents by activating at subthreshold MEMBRANE POTENTIALS, inactivating rapidly, and recovering from inactivation quickly.Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included.Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.Fura-2: A fluorescent calcium chelating agent which is used to study intracellular calcium in tissues.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Thapsigargin: A sesquiterpene lactone found in roots of THAPSIA. It inhibits CA(2+)-TRANSPORTING ATPASE mediated uptake of CALCIUM into SARCOPLASMIC RETICULUM.Heart: The hollow, muscular organ that maintains the circulation of the blood.KCNQ2 Potassium Channel: A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: A subgroup of cyclic nucleotide-regulated ION CHANNELS of the superfamily of pore-loop cation channels that are opened by hyperpolarization rather than depolarization. The ion conducting pore passes SODIUM, CALCIUM, and POTASSIUM cations with a preference for potassium.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Tetraethylammonium: A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme UREASE.Neurotransmitter Agents: Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.Biophysics: The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Lanthanum: Lanthanum. The prototypical element in the rare earth family of metals. It has the atomic symbol La, atomic number 57, and atomic weight 138.91. Lanthanide ion is used in experimental biology as a calcium antagonist; lanthanum oxide improves the optical properties of glass.Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to CADMIUM POISONING.Scorpion Venoms: Venoms from animals of the order Scorpionida of the class Arachnida. They contain neuro- and hemotoxins, enzymes, and various other factors that may release acetylcholine and catecholamines from nerve endings. Of the several protein toxins that have been characterized, most are immunogenic.Muscles: Contractile tissue that produces movement in animals.Nisoldipine: A dihydropyridine calcium channel antagonist that acts as a potent arterial vasodilator and antihypertensive agent. It is also effective in patients with cardiac failure and angina.NAV1.5 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of CARDIOMYOCYTES. Defects in the SCN5A gene, which codes for the alpha subunit of this sodium channel, are associated with a variety of CARDIAC DISEASES that result from loss of sodium channel function.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Intermediate-Conductance Calcium-Activated Potassium Channels: A major class of calcium-activated potassium channels that were originally discovered in ERYTHROCYTES. They are found primarily in non-excitable CELLS and set up electrical gradients for PASSIVE ION TRANSPORT.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.KCNQ3 Potassium Channel: A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is closely related to KCNQ2 POTASSIUM CHANNEL. It is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.Large-Conductance Calcium-Activated Potassium Channel alpha Subunits: The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as CATIONS; those with a negative charge are ANIONS.Ganglia, Spinal: Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Cations: Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.Nerve Tissue ProteinsInositol 1,4,5-Trisphosphate Receptors: Intracellular receptors that bind to INOSITOL 1,4,5-TRISPHOSPHATE and play an important role in its intracellular signaling. Inositol 1,4,5-trisphosphate receptors are calcium channels that release CALCIUM in response to increased levels of inositol 1,4,5-trisphosphate in the CYTOPLASM.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Ryanodine: A methylpyrrole-carboxylate from RYANIA that disrupts the RYANODINE RECEPTOR CALCIUM RELEASE CHANNEL to modify CALCIUM release from SARCOPLASMIC RETICULUM resulting in alteration of MUSCLE CONTRACTION. It was previously used in INSECTICIDES. It is used experimentally in conjunction with THAPSIGARGIN and other inhibitors of CALCIUM ATPASE uptake of calcium into SARCOPLASMIC RETICULUM.Delayed Rectifier Potassium Channels: A group of slow opening and closing voltage-gated potassium channels. Because of their delayed activation kinetics they play an important role in controlling ACTION POTENTIAL duration.Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.NAV1.2 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that mediates the sodium ion permeability of excitable membranes. Defects in the SCN2A gene which codes for the alpha subunit of this sodium channel are associated with benign familial infantile seizures type 3, and early infantile epileptic encephalopathy type 11.Voltage-Gated Sodium Channels: A family of membrane proteins that selectively conduct SODIUM ions due to changes in the TRANSMEMBRANE POTENTIAL DIFFERENCE. They typically have a multimeric structure with a core alpha subunit that defines the sodium channel subtype and several beta subunits that modulate sodium channel activity.Chlorides: Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.Myocytes, Cardiac: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.Charybdotoxin: A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.OxadiazolesLipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.Biophysical Phenomena: The physical characteristics and processes of biological systems.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Intracellular Fluid: The fluid inside CELLS.Animals, Newborn: Refers to animals in the period of time just after birth.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Strontium: An element of the alkaline earth family of metals. It has the atomic symbol Sr, atomic number 38, and atomic weight 87.62.Flunarizine: Flunarizine is a selective calcium entry blocker with calmodulin binding properties and histamine H1 blocking activity. It is effective in the prophylaxis of migraine, occlusive peripheral vascular disease, vertigo of central and peripheral origin, and as an adjuvant in the therapy of epilepsy.Calcimycin: An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Fluorescent Dyes: Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.Calcium Compounds: Inorganic compounds that contain calcium as an integral part of the molecule.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.4-Aminopyridine: One of the POTASSIUM CHANNEL BLOCKERS, with secondary effect on calcium currents, which is used mainly as a research tool and to characterize channel subtypes.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.Cations, Divalent: Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis.Apamin: A highly neurotoxic polypeptide from the venom of the honey bee (Apis mellifera). It consists of 18 amino acids with two disulfide bridges and causes hyperexcitability resulting in convulsions and respiratory paralysis.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.Potassium Chloride: A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.Receptors, Drug: Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Felodipine: A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels.Antihypertensive Agents: Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Sulfonylurea Receptors: ATP-BINDING CASSETTE PROTEINS that are highly conserved and widely expressed in nature. They form an integral part of the ATP-sensitive potassium channel complex which has two intracellular nucleotide folds that bind to sulfonylureas and their analogs.Muscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)Cerebellum: The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Sarcolemma: The excitable plasma membrane of a muscle cell. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.NAV1.4 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of SKELETAL MYOCYTES. Defects in the SCN4A gene, which codes for the alpha subunit of this sodium channel, are associated with several MYOTONIC DISORDERS.Voltage-Dependent Anion Channels: A family of voltage-gated eukaryotic porins that form aqueous channels. They play an essential role in mitochondrial CELL MEMBRANE PERMEABILITY, are often regulated by BCL-2 PROTO-ONCOGENE PROTEINS, and have been implicated in APOPTOSIS.Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.Extracellular Space: Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Azetidinecarboxylic Acid: A proline analog that acts as a stoichiometric replacement of proline. It causes the production of abnormal proteins with impaired biological activity.Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.Mice, Inbred C57BLReceptors, Nicotinic: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.

Functional consequences of mutations in the human alpha1A calcium channel subunit linked to familial hemiplegic migraine. (1/8682)

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

Ionic currents underlying spontaneous action potentials in isolated cerebellar Purkinje neurons. (2/8682)

Acutely dissociated cell bodies of mouse Purkinje neurons spontaneously fired action potentials at approximately 50 Hz (25 degrees C). To directly measure the ionic currents underlying spontaneous activity, we voltage-clamped the cells using prerecorded spontaneous action potentials (spike trains) as voltage commands and used ionic substitution and selective blockers to isolate individual currents. The largest current flowing during the interspike interval was tetrodotoxin-sensitive sodium current (approximately -50 pA between -65 and -60 mV). Although the neurons had large voltage-dependent calcium currents, the net current blocked by cobalt substitution for calcium was outward at all times during spike trains. Thus, the electrical effect of calcium current is apparently dominated by rapidly activated calcium-dependent potassium currents. Under current clamp, all cells continued firing spontaneously (though approximately 30% more slowly) after block of T-type calcium current by mibefradil, and most cells continued to fire after block of all calcium current by cobalt substitution. Although the neurons possessed hyperpolarization-activated cation current (Ih), little current flowed during spike trains, and block by 1 mM cesium had no effect on firing frequency. The outward potassium currents underlying the repolarization of the spikes were completely blocked by 1 mM TEA. These currents deactivated quickly (<1 msec) after each spike. We conclude that the spontaneous firing of Purkinje neuron cell bodies depends mainly on tetrodotoxin-sensitive sodium current flowing between spikes. The high firing rate is promoted by large potassium currents that repolarize the cell rapidly and deactivate quickly, thus preventing strong hyperpolarization and restoring a high input resistance for subsequent depolarization.  (+info)

Somatic recording of GABAergic autoreceptor current in cerebellar stellate and basket cells. (3/8682)

Patch-clamp recordings were performed from stellate and basket cells in rat cerebellar slices. Under somatic voltage clamp, short depolarizing pulses were applied to elicit action potentials in the axon. After the action potential, a bicuculline- and Cd2+-sensitive current transient was observed. A similar response was obtained when eliciting axonal firing by extracellular stimulation. With an isotonic internal Cl- solution, the peak amplitude of this current varied linearly with the holding potential, yielding an extrapolated reversal potential of -20 to 0 mV. Unlike synaptic or autaptic GABAergic currents obtained in the same preparation, the current transient had a slow rise-time and a low variability between trials. This current was blocked when 10 mM BAPTA was included in the recording solution. In some experiments, the current transient elicited axonal action potentials. The current transient was reliably observed in animals aged 12-15 d, with a mean amplitude of 82 pA at -70 mV, but was small and rare in the age group 29-49 d. Numerical simulations could account for all properties of the current transient by assuming that an action potential activates a distributed GABAergic conductance in the axon. The actual conductance is probably restricted to release sites, with an estimated mean presynaptic current response of 10 pA per site (-70 mV, age 12-15 d). We conclude that in developing rats, stellate and basket cell axons have a high density of GABAergic autoreceptors and that a sizable fraction of the corresponding current can be measured from the soma.  (+info)

Activation of human D3 dopamine receptor inhibits P/Q-type calcium channels and secretory activity in AtT-20 cells. (4/8682)

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

Voltage and calcium use the same molecular determinants to inactivate calcium channels. (5/8682)

During sustained depolarization, voltage-gated Ca2+ channels progressively undergo a transition to a nonconducting, inactivated state, preventing Ca2+ overload of the cell. This transition can be triggered either by the membrane potential (voltage-dependent inactivation) or by the consecutive entry of Ca2+ (Ca2+-dependent inactivation), depending on the type of Ca2+ channel. These two types of inactivation are suspected to arise from distinct underlying mechanisms, relying on specific molecular sequences of the different pore-forming Ca2+ channel subunits. Here we report that the voltage-dependent inactivation (of the alpha1A Ca2+ channel) and the Ca2+-dependent inactivation (of the alpha1C Ca2+ channel) are similarly influenced by Ca2+ channel beta subunits. The same molecular determinants of the beta subunit, and therefore the same subunit interactions, influence both types of inactivation. These results strongly suggest that the voltage and the Ca2+-dependent transitions leading to channel inactivation use homologous structures of the different alpha1 subunits and occur through the same molecular process. A model of inactivation taking into account these new data is presented.  (+info)

Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1. (6/8682)

Small and intermediate conductance Ca2+-activated K+ channels play a crucial role in hyperpolarizing the membrane potential of excitable and nonexcitable cells. These channels are exquisitely sensitive to cytoplasmic Ca2+, yet their protein-coding regions do not contain consensus Ca2+-binding motifs. We investigated the involvement of an accessory protein in the Ca2+-dependent gating of hIKCa1, a human intermediate conductance channel expressed in peripheral tissues. Cal- modulin was found to interact strongly with the cytoplasmic carboxyl (C)-tail of hIKCa1 in a yeast two-hybrid system. Deletion analyses defined a requirement for the first 62 amino acids of the C-tail, and the binding of calmodulin to this region did not require Ca2+. The C-tail of hSKCa3, a human neuronal small conductance channel, also bound calmodulin, whereas that of a voltage-gated K+ channel, mKv1.3, did not. Calmodulin co-precipitated with the channel in cell lines transfected with hIKCa1, but not with mKv1. 3-transfected lines. A mutant calmodulin, defective in Ca2+ sensing but retaining binding to the channel, dramatically reduced current amplitudes when co-expressed with hIKCa1 in mammalian cells. Co-expression with varying amounts of wild-type and mutant calmodulin resulted in a dominant-negative suppression of current, consistent with four calmodulin molecules being associated with the channel. Taken together, our results suggest that Ca2+-calmodulin-induced conformational changes in all four subunits are necessary for the channel to open.  (+info)

Characterization of elementary Ca2+ release signals in NGF-differentiated PC12 cells and hippocampal neurons. (7/8682)

Elementary Ca2+ release signals in nerve growth factor- (NGF-) differentiated PC12 cells and hippocampal neurons, functionally analogous to the "Ca2+ sparks" and "Ca2+ puffs" identified in other cell types, were characterized by confocal microscopy. They either occurred spontaneously or could be activated by caffeine and metabotropic agonists. The release events were dissimilar to the sparks and puffs described so far, as many arose from clusters of both ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (InsP3Rs). Increasing either the stimulus strength or loading of the intracellular stores enhanced the frequency of and coupling between elementary release sites and evoked global Ca2+ signals. In the PC12 cells, the elementary Ca2+ release preferentially occurred around the branch points. Spatio-temporal recruitment of such elementary release events may regulate neuronal activities.  (+info)

Control and assessment of the uterus and cervix during pregnancy and labour. (8/8682)

Preterm labour and resultant preterm birth are the most important problems in perinatology. Countless efforts have failed to establish a single effective treatment of preterm labour, partly because the mechanisms regulating the uterus and cervix during pregnancy are not well understood. New knowledge is needed to inhibit early progression of labour (uterine contractility and cervical ripening), and adequate quantitative tools to evaluate the uterus and cervix during pregnancy are lacking. In this review, we outline studies showing that the uterus (myometrium) and cervix pass through a conditioning step in preparation for labour. This step is not easily identifiable with present methods to assess the uterus or cervix. In the uterus, this seemingly irreversible step consists of changes in the electrical properties to make muscle more excitable and responsive to produce forceful contractions. In the cervix, the step consists of softening of the connective tissue components. Progesterone appears to have a dominant role in controlling both the uterus and cervix, as antiprogestins induce early, preterm conditioning leading to preterm labour. Apparently, nitric oxide (NO) also controls conditioning of the uterus and cervix. In the uterus, NO, in concert with progesterone, inhibits uterine contractility. At term, NO production by the uterus and placenta are decreased and allow labour to progress. In contrast, NO in the cervix increases at the end of pregnancy and it may be the final pathway for stimulating cervical ripening by activation of metalloenzymes. The progress of labour can be assessed non-invasively using electromyographic (EMG) signals from the uterus (the driving force for contractility) recorded from the abdominal surface. Uterine EMG bursts detected in this manner characterize uterine contractile events during human and animal pregnancy. A low uterine EMG activity, measured transabdominally throughout most of pregnancy, rises dramatically during labour. EMG activity also increases substantially during preterm labour in humans and rats. This method may be used one day to predict impending preterm labour and identify control steps and treatments. A quantitative method also assesses the cervix, using an optical device which measures collagen fluorescence in the cervix. The collascope estimates cervical collagen content from a fluorescent signal generated when collagen cross-links are illuminated with excitation light of about 340 nm. The system has proved useful in rats and humans at various stages of pregnancy, and indicates that cervical softening occurs progressively in the last one-third of pregnancy. In rats, collascope readings correlate with resistance measurements made in the isolated cervix, which may help to assess cervical function during pregnancy, and indicate control and treatments.  (+info)

Live-cell imaging allows for the in-depth study of activities occurring within living cells. The understanding of these complex interactions has wide ranging implications to many biomedical applications [1]. As the techniques used in live-cell imaging have improved, they have become an important component of monitoring the interactions within and among cells throughout their lifecycle [2, 3] . Several probes have been developed in relation to these endeavors, [4-6], and in turn, we have created T-Time, a repository of T cell images using a novel tag developed in [7].. T cells are lymphocytes that play a central role in cell-mediated immunity to foreign pathogens. Dysregulated T cell responses are implicated in numerous chronic conditions ranging from severe combined immunodeficiency (SCID) to autoimmunity and cancer. T cells migrate extensively throughout the body to enable proper immune function. This migration is the focus of extensive research and has motivated the development of ...
In the present study we have investigated the role of inositol 1,4,5-trisphosphate (IP3), functional IP3 receptors (IP3Rs) and the human homologue of the Drosophila transient receptor potential (Trp) channel, human Trp1 (hTrp1), in store-mediated Ca2+ entry (SMCE) in human platelets. Inhibition of IP3 recycling using Li+, or the inhibition of IP3Rs using xestospongin C, both resulted in the inhibition of SMCE activation following Ca2+ store depletion using thapsigargin. Co-immunoprecipitation experiments indicated that endogenously expressed hTrp1 couples with IP3R type II, but not types I or III, in platelets with depleted intracellular Ca2+ stores, but not in control, undepleted cells. These results provide strong evidence for the activation of SMCE by conformational coupling involving de novo association between IP3Rs and a plasma membrane channel in normal human cells.. ...
A calcium channel opener is a type of drug which facilitates ion transmission through calcium channels. An example is Bay K8644, which is an analogue of nifedipine that specifically and directly activates L-type voltage-dependent calcium channels. In contrast to Bay K8644, which is not for clinical use, Ambroxol is a frequently used mucolytic drug that triggers lysosomal secretion by mobilizing calcium from acidic calcium stores. This effect does most likely not occur by a direct interaction between the drug and a lysosomal calcium channel, but indirectly by neutralizing the acidic pH within lysosomes. Calcium permeable ion channels in lysosomal membranes that may be activated by a luminal pH increase include two pore channels (TPCs), mucolipin TRP channels (TRPMLs) and purinergic receptors of the P2X channel type. Calcium channel blocker Schramm M, Thomas G, Towart R, Franckowiak G (1983). "Activation of calcium channels by novel 1,4-dihydropyridines. A new mechanism for positive inotropics or ...
Voltage-dependent calcium channels represent a major pathway of calcium entry into neurons, where they participate actively to cell excitability and to the molecular processes of synaptic transmission. For that reason, they have been the direct or indirect pharmacological targets of analgesics and this long before their implication in the physiology of nociception had been demonstrated. These last years, the still more refined molecular characterization of these channels and their associated regulatory subunits and the demonstration of their implication in nociceptive processes indicates that these structures are prime pharmacological targets for the management of pain. Herein, we detail the recent breakthroughs on calcium channel structure, function and pharmacology, review the implication of calcium channels in the transmission of nociception, and evaluate their importance as targets for the treatment of pain perception. The search for specific inhibitors of voltage-dependent calcium channels appears
Calcium release-activated calcium channels (CRAC) control influx of calcium in human T lymphocytes. Hour-long calcium elevations are necessary for efficient gene expression during T cell activation and proliferation. We report here that, the time course for store-operated Ca2+ entry is short-lived (3-4 min) and therefore, cannot account for the prolonged Ca2+ elevations necessary for NFAT translocation into nucleus. Previous findings strongly suggest that T cell activation is accompanied by cytosolic alkalinization. Here, we show that pH changes in Jurkat T cells following activation with mitogenic lectin, phytohemagglutinin (PHA), depends on the length of time of exposure and the concentration (potency) of the mitogen. For full understanding of ion fluxes involved in this process, it is important to distinguish CRAC channel subtype functions in these cells during activation as well as elucidate the pH mediated changes in Ca2+. In some experiments we show low pH with high concentrations of PHA. We also
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TY - JOUR. T1 - Restoration of motor defects caused by loss of drosophila TDP-43 by expression of the voltage-gated calcium channel, cacophony, in central neurons. AU - Lembke, Kayly M.. AU - Scudder, Charles. AU - Morton, David. PY - 2017/9/27. Y1 - 2017/9/27. N2 - Defects in the RNA-binding protein, TDP-43, are known to cause a variety of neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal lobar dementia. A variety of experimental systems have shown that neurons are sensitive to TDP-43 expression levels, yet the specific functional defects resulting from TDP-43 dysregulation have not been well described. Using the Drosophila TDP-43 ortholog TBPH, we previously showed that TBPH-null animals display locomotion defects as third instar larvae. Furthermore, loss of TBPH caused a reduction in cacophony, a Type II voltage-gated calcium channel, expression and that genetically restoring cacophony in motor neurons in TBPH mutant animals was sufficient to rescue the ...
Voltage-dependent calcium channel subunit alpha-2/delta-1 (CA2D1) antibody | P54289 | Voltage-dependent calcium channel subunit alpha-2/delta-1, Voltage-gated calcium channel subunit alpha-2/delta-1, CACNL2A, CCHL2A, MHS3
RecName: Full=Voltage-dependent calcium channel subunit alpha-2/delta-4;AltName: Full=Voltage-gated calcium channel subunit alpha-2/delta-4;Contains: RecName: Full=Voltage-dependent calcium channel subunit alpha-2-4;Contains: RecName: Full=Voltage-depen ...
Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (e.g., muscle, glial cells, neurons, etc.) with a permeability to the calcium ion Ca2+. These channels are slightly permeable to sodium ions, so they are also called Ca2+-Na+ channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions. At physiologic or resting membrane potential, VGCCs are normally closed. They are activated (i.e., opened) at depolarized membrane potentials and this is the source of the "voltage-gated" epithet. The concentration of calcium (Ca2+ ions) is normally several thousand times higher outside the cell than inside. Activation of particular VGCCs allows Ca2+ to rush into the cell, which, depending on the cell type, results in activation of calcium-sensitive potassium channels, muscular contraction, excitation of neurons, ...
Voltage-gated calcium channels are multi-subunit membrane proteins which transduce depolarization into cellular functions like excitation-contraction coupling in muscle or neurotransmitter release in neurons. The auxiliary β subunits function in membrane targeting of the channel and modulation of its gating properties. However, whether β subunits can reversibly interact with, and thus differentially modulate channels in the membrane is still unresolved. Here we applied fluorescence recovery after photobleaching (FRAP) of GFP-tagged α1 and β subunits expressed in dysgenic myotubes to study the relative dynamics of these calcium channel subunits for the first time in a native functional signaling complex. Identical fluorescence recovery rates of both subunits indicate stable interactions, distinct rates dynamic interactions. Whereas the skeletal muscle β1a isoform formed stable complexes with CaV1.1 and CaV1.2, the non-skeletal muscle β2a and β4b isoforms dynamically interacted with both ...
Frequency of genetic polymorphism of calcium channels gene CACNA1C in healthy individuals and patients with arterial hypertension
Definition of calcium channel blocking agent in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is calcium channel blocking agent? Meaning of calcium channel blocking agent as a finance term. What does calcium channel blocking agent mean in finance?
Voltage-dependent N-type calcium channel subunit alpha-1B (Brain calcium channel III) (BIII) (Calcium channel; L type; alpha-1 polypeptide isoform 5) (Voltage-gated calcium channel subunit alpha Cav2.2 ...
N-type calcium channels belong to the family of voltage gated calcium channels , which open in response to membrane depolarisation. These channels are responsible for the calcium influx that triggers neurotransmitter release at presynaptic terminals. N - type channels are particularly important in mediating neurotransmitter release at the presynaptic terminals of peripheral sensory neurons and have been implicated i n neuropathic pain. Understanding the regulation of N - type channels is critical to the development of treatments that target these channels. Until now it has been difficult to directly investigate the regulation of their expression at the cell surface due to the inability to selectively visualise channels at the surface. Although N - type channels are thought to consist of a Ca v 2.2, α 2 δ and β subunits, there is uncertainty over whether the pore forming Ca v 2.2 subunit does indeed interact with α 2 δ at the cell surface. The work in this thesis has yielded two tagged ...
Alternative splicing of a pair of mutually exclusive exons (exon 37a and 37b) of the P/Q-type Ca2+ channels produces two different splice variants in the EF-hand region, namely Cav2.1[EFa] and Cav2.1[EFb] channels. Using isoform-specific antibodies against Cav2.1[EFa] and Cav2.1[EFb] channels, we show that Cav2.1[EFa] and Cav2.1[EFb] channels are differentially localized in subcellular compartments of hippocampal, cerebellar and cortical neurons. Cav2.1[EFb] channels show somatic, proximal and distal dendritic localization while Cav2.1[EFa] channels are expressed in the cell bodies, proximal dendrites as well as presynaptic terminals. The distinct subcellular localization of Cav2.1[EFa] and Cav2.1[EFb] channels suggests compartmentalized roles of voltage-gated Ca2+ channels in neurotransmitter release and generation of synaptic plasticity. In addition, a yeast-two-hybrid screen was performed to find potential interacting proteins with the EF-hand of the Cav2.1[EFa] channel. The screen reveals ...
Foto: MUI/Presseabteilung; Gerald Obermair mit seinem Team PhD - Student Clemens Schöpf und Stefanie Geisler ,, Presseartikel mypoint. The family of α1 subunits consists of 10 genes, seven of which constitute the high-voltage-activated calcium channels of the CaV1 and CaV2 subgroups (α1A to α1F and α1S). With the exception of two specific α1 subunits expressed in skeletal muscle (see research by The Flucher Lab) and in the retina all isoforms are expressed in the nervous system.. Regarding the auxiliary subunits all of the four β subunits and three of the four α2δ subunits are found in the brain. Because all α1, β, and α2δ subunits can form functional channel complexes with each other, this yields the theoretical number of 60 different brain calcium channels (5 α1 X 4 β X 3 α2δ) not considering the existence of multiple splices of each protein! In our research we address the question why nerve cells express so many different calcium channels subunits and whether individual ...
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the high-voltage activated (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function ...
Background Antigen stimulation of immune cells triggers Ca2+ entry through Ca2+ release-activated Ca2+(CRAC) channels, promoting an immune response to pathogens. Defects in a CRAC (Orai) channel in...
Mast cell activation involves cross-linking of IgE receptors followed by phosphorylation of the non-receptor tyrosine kinase Syk. This results in activation of the plasma membrane-bound enzyme phospholipase Cgamma1, which hydrolyzes the minor membrane phospholipid phosphatidylinositol 4,5-bisphosphate to generate diacylglycerol and inositol trisphosphate. Inositol trisphosphate raises cytoplasmic Ca2+ concentration by releasing Ca2+ from intracellular stores. This Ca2+ release phase is accompanied by sustained Ca2+ influx through store-operated Ca2+ release-activated Ca2+ (CRAC) channels. Here, we find that engagement of IgE receptors activates Syk, and this leads to Ca2+ release from stores followed by Ca2+ influx. The Ca2+ influx phase then sustains Syk activity. The Ca2+ influx pathway activated by these receptors was identified as the CRAC channel, because pharmacological block of the channels with either a low concentration of Gd3+ or exposure to the novel CRAC channel blocker 3-fluoropyridine-4
TY - JOUR. T1 - Store-independent activation of orai1 by SPCA2 in mammary tumors. AU - Feng, Mingye. AU - Grice, Desma M.. AU - Faddy, Helen M.. AU - Nguyen, Nguyen. AU - Leitch, Sharon. AU - Wang, Yingyu. AU - Muend, Sabina. AU - Kenny, Paraic A.. AU - Sukumar, Saraswati. AU - Roberts-Thomson, Sarah J.. AU - Monteith, Gregory R.. AU - Rao, Rajini. PY - 2010/10/1. Y1 - 2010/10/1. N2 - Ca2+ is an essential and ubiquitous second messenger. Changes in cytosolic Ca2+ trigger events critical for tumorigenesis, such as cellular motility, proliferation, and apoptosis. We show that an isoform of Secretory Pathway Ca2+-ATPase, SPCA2, is upregulated in breast cancer-derived cells and human breast tumors, and suppression of SPCA2 attenuates basal Ca2+ levels and tumorigenicity. Contrary to its conventional role in Golgi Ca2+ sequestration, expression of SPCA2 increased Ca2+ influx by a mechanism dependent on the store-operated Ca2+ channel Orai1. Unexpectedly, SPCA2-Orai1 signaling was independent of ER ...
Elevation in cytosolic calcium, [Ca2+]i, is an essential step in numerous physiological and pathophysiological signal transduction events. Ion channels allowing for the entry of extracellular Ca2+ into the cytosol are the principal source of increased [Ca2+]i. In nonexcitable cells, store-operated calcium (SOC), and to a lesser extent, receptor-operated calcium (ROC), entry channels represent the main source of calcium entry.1,2 Although it is generally recognized that SOC entry occurs through Ca2+-selective and nonselective channels, the molecular makeup, regulation, and downstream targets of specific channels remain to be determined.. In endothelial cells, activation of SOC entry contributes to the formation of intercellular gaps, leading to endothelial barrier disruption,3-5 a common factor in the development and progression of systemic and pulmonary diseases, including hypertension, atherosclerosis, and acute respiratory distress syndrome. It is therefore therapeutically desirable to ...
Reduced pancreatic b-cell function or mass is the critical problem in developing diabetes. Insulin release from b-cells depends on Ca2+ influx through high voltage- gated Ca2+ channels (HVCCs). Ca2+ influx also regulates insulin synthesis and insulin granule priming and contributes to β-cell electrical activity. The HVCCs aremultisubunit protein complexes composed of a pore-forming a1 and auxiliary β and α2δ subunits. α2δ is a key regulator of membrane incorporation and function of HVCCs. Here we show that genetic deletion of α2δ-1, the dominant α 2δ subunit in pancreatic islets, results in glucose intolerance and diabetes without affecting insulin sensitivity. Lack of the α 2δ-1 subunit reduces the Ca2+ currents through all HVCC isoforms expressed in b-cells equally in male and female mice. The reduced Ca2+ influx alters the kinetics and amplitude of the global Ca2+ response to glucose in pancreatic islets and significantly reduces insulin release in both sexes. The progression of ...
Store-operated Ca2+ channels in the plasma membrane (PM) are activated by the depletion of Ca2+ from the endoplasmic reticulum (ER) and constitute a widespread and highly conserved Ca2+ influx pathway. After store emptying, the ER Ca2+ sensor STIM1 forms multimers, which then migrate to ER-PM junctions where they activate the Ca2+ release-activated Ca2+ channel Orai1. Movement of an intracellular protein to such specialized sites where it gates an ion channel is without precedence, but the fundamental question of how STIM1 migrates remains unresolved. Here, we show that trafficking of STIM1 to ER-PM junctions and subsequent Ca2+ release-activated Ca2+ channel activity is impaired following mitochondrial depolarization. We identify the dynamin-related mitochondrial protein mitofusin 2, mutations of which causes the inherited neurodegenerative disease Charcot-Marie-Tooth IIa in humans, as an important component of this mechanism. Our results reveal a molecular mechanism whereby a mitochondrial fusion
Calcium (Ca2+) is an essential signaling messenger in every eukaryotic cell, regulating diverse and kinetically distinct cellular phenomena in health and disease. Sarco/endoplasmic reticulum (SR/ER) luminal store-dependent Ca2+ influx through plasma membrane (PM) Ca2+ release activated Ca2+ (CRAC) channels is a vital Ca2+ entry pathway mediating sustained cytosolic Ca2+ elevations. The molecular players that mediate this store-operated Ca2+ entry (SOCE) include the stromal interaction molecules (STIM)s which sense changes in SR/ER luminal Ca2+ levels and the Orai proteins which constitute the PM Ca2+ channel pore. Upon luminal Ca2+ store depletion, STIMs oligomerize and translocate to the SR/ER-PM junctions where they recruit and activate the Orai channels, forming a CRAC channel complex. My research applies structural biology (i.e. solution nuclear magnetic resonance spectroscopy and X-ray crystallography), biophysical methodologies (i.e. optical spectroscopies, calorimetry, chromatography, ...
Ca2+ flux into mitochondria is an important regulator of cytoplasmic Ca2+ signals, energy production and cell death pathways. Ca2+ uptake can occur through the recently discovered mitochondrial uniporter channel (MCU) but whether the MCU is involved in shaping Ca2+ signals and downstream responses to physiological levels of receptor stimulation is unknown. Here, we show that modest stimulation of leukotriene receptors with the pro-inflammatory signal LTC4 evokes a series of cytoplasmic Ca2+ oscillations that are rapidly and faithfully propagated into mitochondrial matrix. Knockdown of MCU or mitochondrial depolarisation, to reduce the driving force for Ca2+ entry into the matrix, prevents the mitochondrial Ca2+ rise and accelerates run down of the oscillations. The loss of cytoplasmic Ca2+ oscillations appeared to be a consequence of enhanced Ca2+-dependent inactivation of InsP3 receptors, which arose from the loss of mitochondrial Ca2+ buffering. Ca2+ dependent gene expression in response to
Orai1 antibody (ORAI calcium release-activated calcium modulator 1) for ELISA, ICC/IF, IHC-P, WB. Anti-Orai1 pAb (GTX85057) is tested in Human, Mouse samples. 100% Ab-Assurance.
Ca(2+)-dependent gene expression is critical for cell growth, proliferation, plasticity, and adaptation [1-3]. Because a common mechanism in vertebrates linking cytoplasmic Ca(2+) signals with activation of protein synthesis involves the nuclear factor of activated T cells (NFAT) family of transcription factors [4, 5], we have quantified protein expression in single cells following physiological Ca(2+) signals by using NFAT-driven expression of a genetically encoded fluorescent protein. We find that gene expression following CRAC channel activation is an all-or-nothing event over a range of stimulus intensities. Increasing agonist concentration recruits more cells but each responding cell does so in an essentially digital manner. Furthermore, Ca(2+)-dependent gene expression shows both short-term memory and strong synergy, where two pulses of agonist, which are ineffectual individually, robustly activate gene expression provided that the time interval between them is short. Such temporal filtering
RGK regulation of voltage-gated calcium channels. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
We hypothesized that the store-operated calcium entry (SOCE) channel, Orai1, participates in the activation of Th17 cells and influences renal injury. In rats, following renal ischemia/reperfusion (I/R), there was a rapid and sustained influx of Orai1+ CD4 T cells and IL-17 expression was restricted to Orai1+ cells. When kidney CD4+ cells of post-acute kidney injury (post-AKI) rats were stimulated with angiotensin II and elevated Na+ (10-7 M/170 mM) in vitro, there was an enhanced response in intracellular Ca2+ and IL-17 expression, which was blocked by SOCE inhibitors 2APB, YM58483/BTP2, or AnCoA4. In vivo, YM58483/BTP2 (1 mg/kg) attenuated IL-17+ cell activation, inflammation, and severity of AKI following either I/R or intramuscular glycerol injection. Rats treated with high-salt diet (5-9 weeks after I/R) manifested progressive disease indicated by enhanced inflammation, fibrosis, and impaired renal function. These responses were significantly attenuated by YM58483/BTP2. In peripheral blood ...
We hypothesized that the store-operated calcium entry (SOCE) channel, Orai1, participates in the activation of Th17 cells and influences renal injury. In rats, following renal ischemia/reperfusion (I/R), there was a rapid and sustained influx of Orai1+ CD4 T cells and IL-17 expression was restricted to Orai1+ cells. When kidney CD4+ cells of post-acute kidney injury (post-AKI) rats were stimulated with angiotensin II and elevated Na+ (10-7 M/170 mM) in vitro, there was an enhanced response in intracellular Ca2+ and IL-17 expression, which was blocked by SOCE inhibitors 2APB, YM58483/BTP2, or AnCoA4. In vivo, YM58483/BTP2 (1 mg/kg) attenuated IL-17+ cell activation, inflammation, and severity of AKI following either I/R or intramuscular glycerol injection. Rats treated with high-salt diet (5-9 weeks after I/R) manifested progressive disease indicated by enhanced inflammation, fibrosis, and impaired renal function. These responses were significantly attenuated by YM58483/BTP2. In peripheral blood ...
The IUPHAR/BPS Guide to Pharmacology. Cav1.3 - Voltage-gated calcium channels. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
ENCODES a protein that exhibits low voltage-gated calcium channel activity (ortholog); INVOLVED IN neuronal action potential; sleep; calcium ion import (ortholog); PARTICIPATES IN calcium transport pathway; calcium/calcium-mediated signaling pathway; mitogen activated protein kinase signaling pathway; INTERACTS WITH bisphenol A; raloxifene; tetraphene
Concentrations of calcium within mitochondria are tightly regulated and modulate physiological mitochondrial functions, including control of metabolism and cell death. Sancak et al. complete the molecular characterization of the mitochondrial calcium uniporter (MCU), the multicomponent channel that allows concentration of calcium within the organelle. They identified a small protein termed "essential MCU regulator"-or EMRE-which was required for calcium transport activity of the fully assembled uniporter.. Y. Sancak, A. L. Markhard, T. Kitami, E. Kovács-Bogdán, K. J. Kamer, N. D. Udeshi, S. A. Carr, D. Chaudhuri, D. E. Clapham, A. A. Li, S. E. Calvo, O. Goldberger, V. K. Mootha, EMRE is an essential component of the mitochondrial calcium uniporter complex. Science 342, 1379-1382 (2013). [Abstract] [Full Text] ...
To unravel the evolutionarily conserved genetic network underlying energy homeostasis, we performed a systematic in vivo gene knockdown screen in D...
Mouse monoclonal Stromal interaction molecule 1 antibody validated for WB, IP, IHC, ICC, Flow Cyt, ICC/IF and tested in Human. Referenced in 2 publications and…
Mouse monoclonal Stromal interaction molecule 1 antibody [CDN3H4] validated for WB, IP and tested in Mouse and Rat. Referenced in 1 publication. Immunogen…
Stromal interaction molecule 1兔单克隆抗体[EPR3414](ab108994)可与小鼠, 大鼠, 人样本反应并经WB, IP, IHC实验严格验证。中国75%以上现货。
GRC is a Ca2+-permeable nonselective cation channel belonging to the TRP channel family, which translocates from the cell interior to the surface in response to growth factors (Kanzaki et al., 1999; Boels et al., 2001). GRC is normally expressed in adult striated muscles, with low expression in the sarcolemma except in cardiac intercalated discs (Fig. 1). In normal hamster myotubes, sarcolemmal GRC expression was transiently elevated only on the first day of cell fusion, whereas in BIO14.6 myotubes, this initial expression continued (Fig. 2; unpublished data). Intriguingly, in normal myotubes, cell stretch increased sarcolemmal GRC expression, which required entry of external Ca2+ (Fig. 2, b and c). This triggering Ca2+ could have entered via a low level of GRC initially present in the sarcolemma. However, little is known as to what initially triggers the surface translocation of GRC during the formation of myotubes. The situation was somewhat similar in the case of GRC-transfected CHO cells; an ...
Catalysis of facilitated diffusion of a calcium ion (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism.
Peptides , Prion Protein (PrP) Fragments , PrP (106-126); This peptide increases membrane microviscosity, intracellular Ca2+ concentration and cell migration in circulating leucocytes, and oxygen production in monocytes and neutrophils. It also induces apoptotic cell death and impairment of L-type voltage-sensitive calcium channel activity in the GH3 cell lines. PrP (106 126) stimulates leucocyte migration in a dose-dependent manner.; KTNMKHMAGAAAAGAVVGGLG; H-Lys-Thr-Asn-Met-Lys-His-Met-Ala-Gly-Ala-Ala-Ala-Ala-Gly-Ala-Val-Val-Gly-Gly-Leu-Gly-OH
A main challenge in stem-cell mediated regenerative medication is the advancement of described culture systems for the maintenance of clinical-grade individual embryonic stem (hES) cells. laboratories possess concentrated on developing described circumstances for hES cell lifestyle4C9. One technique provides been to replace nonhuman items, i.age. pet sera and mouse embryonic Angiotensin (1-7) IC50 fibroblast (MEF) […]. Read More ». ...
Can anyone recommend any newsgroups dealing with calcium channel of SR? Thank you in advance for your help. ssultang (in english, sugar ...
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Complete information for STIM2 gene (Protein Coding), Stromal Interaction Molecule 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
cacophony - Meaning in Kannada, what is meaning of common in Kannada dictionary, audio pronunciation, synonyms and definitions of common in Kannada and English.
The TG-insensitive store senses Ca2+ near CRAC channels. Experimental conditions and analysis were identical to Fig. 2 with the exception that conditions durin
Interaction of the endoplasmic reticulum (ER) calcium sensor STIM1 with Orai channels at the plasma membrane mediates cellular calcium influx after its depletion from ER stores. New data show that adenylyl cyclase 6 (ADCY6) is an Orai‐independent STIM1 interactor at ER-plasma membrane junctions with a critical role in melanogenesis.. ...
Previous work compiled from TEM studies has shown that larger ribbons have more ribbon-associated vesicles (Nouvian et al., 2006; Matthews and Fuchs, 2010; Graydon et al., 2011). Likewise, our TEM data also indicate that enlarged ribbons have an increased number of tethered vesicles compared with WT ribbons, which predicts the potential for an increase in vesicle fusion (Fig. 1J). In addition, our measurements of whole-cell calcium currents and ribbon-localized calcium signals found that calcium responses were elevated in hair cells with enlarged ribbons (Figs. 4A,B, 6E,E′). Yet despite larger calcium currents and more tethered vesicles at enlarged ribbons, we observed no increase in evoked activity and a significant reduction in spontaneous vesicle fusion (Fig. 7). These results are similar to what has been observed in mammalian auditory IHCs, where larger ribbons are correlated with elevated calcium currents and less spontaneous activity (Taberner and Liberman, 2005; Liberman et al., ...
Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent…
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 ...
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The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
1 Answer (question resolved) - Posted in: cartia xt, high blood pressure - Answer: Cartia XT is an extended release calcium channel beta blocker. I ...
Lyrics to Savage by Cacophony: He is one lier / Im watch this / Dont go I haunting take / Im a savior / We take are you / Dont run you
Homo sapiens calcium channel, voltage-dependent, alpha 1G subunit (CACNA1G), transcript variant 13, mRNA. (H00008913-R13) - Products - Abnova
Homo sapiens calcium channel, voltage-dependent, alpha 1G subunit (CACNA1G), transcript variant 6, mRNA. (H00008913-R08) - Products - Abnova
Read "Ca2+ Calmodulin Kinase and Calcineurin Mediate IGF-1-induced Skeletal Muscle Dihydropyridine Receptor α1S Transcription, The Journal of Membrane Biology" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the high-voltage activated (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle ...
The TRPC (transient receptor potential canonical) proteins are activated in response to agonist-stimulated PIP2 (phosphatidylinositol 4,5-bisphosphate) hydrolysis and have been suggested as candidate components of the elusive SOC (store-operated calcium channel). TRPC1 is currently the strongest candidate component of SOC. Endogenous TRPC1 has been shown to contribute to SOCE (store-operated calcium entry) in several different cell types. However, the mechanisms involved in the regulation of TRPC1 and its exact physiological function have yet to be established. Studies from our laboratory and several others have demonstrated that TRPC1 is assembled in a signalling complex with key calcium signalling proteins in functionally specific plasma membrane microdomains. Furthermore, critical interactions between TRPC1 monomers as well as interactions between TRPC1 and other proteins determine the surface expression and function of TRPC1-containing channels. Recent studies have revealed novel regulators ...
Definition of receptor-operated channel in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is receptor-operated channel? Meaning of receptor-operated channel as a legal term. What does receptor-operated channel mean in law?
The regulation of transmitter release at the neuromuscular junction is tightly regulated by the influx of calcium in the presynaptic nerve terminal. Interestingly, the probability that release sites at the neuromuscular junction will liberate transmitter during each action potential is very low. The reasons for this low probability of release are not well understood. To test the hypothesis that individual N-type calcium channels open with a low probability, single channel recordings of N-type voltage-gated calcium channels were performed. Using this approach I determined the conductance of these channels, their probability of gating during an action potential waveform, and the magnitude of calcium flux during a single channel opening. I conclude from these studies that N-type voltage-gated calcium channels have a very low probability of opening (< 5%) during an action potential and the characteristics of calcium entry during single channel openings can help to explain the low probability of ...
Looking for online definition of calcium channel, voltage-dependent, gamma subunit 6 in the Medical Dictionary? calcium channel, voltage-dependent, gamma subunit 6 explanation free. What is calcium channel, voltage-dependent, gamma subunit 6? Meaning of calcium channel, voltage-dependent, gamma subunit 6 medical term. What does calcium channel, voltage-dependent, gamma subunit 6 mean?
Low-voltage-activated calcium channels in the lamprey locomotor network: simulation and experiment. J. Neurophysiol. 77: 1795-1812, 1997. To evaluate the role of low-voltage-activated (LVA) calcium channels in the lamprey spinal locomotor network, a previous computer simulation model has been extended to include LVA calcium channels. It is also of interest to explore the consequences of a LVA conductance for the electrical behavior of the single neuron. The LVA calcium channel was modeled with voltage-dependent activation and inactivation using the m 3 h form, following a Hodgkin-Huxley paradigm. Experimental data from lamprey neurons was used to provide parameter values of the single cell model. The presence of a LVA calcium conductance in the model could account for the occurrence of a rebound depolarization in the simulation model. The influence of holding potential on the occurrence of a rebound as well the latency at which it is elicited was investigated and compared with previous ...
RecName: Full=Voltage-dependent P/Q-type calcium channel subunit alpha-1A;AltName: Full=Voltage-gated calcium channel subunit alpha Cav2.1;AltName: Full=Calcium channel, L type, alpha-1 polypeptide isoform 4;AltName: Full=Brain calcium channel I; Short=BI ...
N-Type Calcium Channels: CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.
The present study demonstrated that the opening of the L-type Ca2+ channels was increased in arterial smooth muscle cells from SHR compared with WKY. However, the single-channel conductance and open time did not differ between SHR and WKY. Thus, an increased opening of the single channels would contribute greatly to the increased amplitude of the whole-cell current.. The unitary inward current recorded in the present study was considered to be L-type Ca2+ channel currents from the following findings: (1) single-channel conductance and open time were basically the same as those of the L-type Ca2+ channel in other arterial tissues studied10,11,13; (2) the holding potential was −40 mV, which inactivated the T-type Ca2+ channels as well as Na+ channels10; and (3) the channel opening disappeared with the application of nifedipine, suggesting that the channel is sensitive to dihydropyridines.10 11 Whole-cell amplitude (I) consisted of several parameters, such as the amplitude of the single-channel ...
This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-profit organization that is leading Canadas national genomics strategy with funding from the federal government. Maintenance, support, and commercial licensing is provided by OMx Personal Health Analytics, Inc. Designed by Educe Design & Innovation Inc. ...
This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-profit organization that is leading Canadas national genomics strategy with funding from the federal government. Maintenance, support, and commercial licensing is provided by OMx Personal Health Analytics, Inc. Designed by Educe Design & Innovation Inc. ...
title: Regulation of phagocytosis and cytokine secretion by store-operated calcium entry in primary isolated murine microglia, doi: 10.1016/j.cellsig.2014.11.003, category: Article
TY - JOUR. T1 - Domain III regulates N-type (Ca V2.2) calcium channel closing kinetics. AU - Yarotskyy, Viktor. AU - Gao, Guofeng. AU - Peterson, Blaise Z.. AU - Elmslie, Keith S.. PY - 2012/4/1. Y1 - 2012/4/1. N2 - Ca V2.2 (N-type) and Ca V1.2 (L-type) calcium channels gate differently in response to membrane depolarization, which is critical to the unique physiological functions mediated by these channels. We wondered if the source for these differences could be identified. As a first step, we examined the effect of domain exchange between N-type and L-type channels on activationdeactivation kinetics, which were significantly different between these channels. Kinetic analysis of chimeric channels revealed N-channellike deactivation for all chimeric channels containing N-channel domain III, while activation appeared to be a more distributed function across domains. This led us to hypothesize that domain III was an important regulator of N-channel closing. This idea was further examined with ...
Research Summary. Calcium channels and the regulation of secretion Calcium ions entering cells through multiple types of voltage-dependent calcium channels regulate a variety of physiological processes including synaptic transmission, muscle contraction, regulation of calcium-dependent ion channels, regulation of calcium dependent enzymes etc. In addition to allowing a critical second messenger, calcium, to enter cells, calcium channels also play an important role in the generation of action potentials. Our lab studies the biophysical and pharmacological properties of various calcium channels and their regulation by neurotransmitters and second messengers. We also use molecular biological tools to isolate novel calcium channel subunits. Of all the physiological properties regulated by calcium channels none is more important than the regulation of secretion that occurs at synapses or in secretory cells. Our lab studies secretion in both chromaffin and PC12 cells triggered by the activation of ...
One significant controversy surrounding TRPC channels is if they participate in store-operated Ca2+ entry (SOCE) or if they are more specialized for receptor-operated Ca2+ entry (ROCE) (Figure 2). SOCE refers to refilling of internal Ca2+ stores in the endoplasmic/sarcoplasmic reticulum (ER/SR) after depletion, such as after prolonged IP3 stimulation. SOCE proceeds through the activity of an undefined plasma membrane channel,34,35 at first attributed to TRPC but later refined to Orai1 (Ca2+ release-activated channel protein). Store depletion can be experimentally mimicked by inhibiting SR/ER Ca2+-ATPase (SERCA) (with thapsigargin or cyclopiazonic acid), while stimulating ER Ca2+ release with a GPCR ligand or by treating cells with Ca2+ ionophores. Although it remains controversial, evidence has shown that TRPC channels can function in SOCE, results that have been substantiated in gene-deleted or transgenic mice.36,-,38 For example, deletion of Trpc4 results in decreased SOCE activity in ...
TY - JOUR. T1 - Ca2+ channel subtypes and pharmacology in the kidney. AU - Hayashi, Koichi. AU - Wakino, Shu. AU - Sugano, Naoki. AU - Ozawa, Yuri. AU - Homma, Koichiro. AU - Saruta, Takao. PY - 2007/2/1. Y1 - 2007/2/1. N2 - A large body of evidence has accrued indicating that voltage-gated Ca channel subtypes, including L-, T-, N-, and P/Q-type, are present within renal vascular and tubular tissues, and the blockade of these Ca channels produces diverse actions on renal microcirculation. Because nifedipine acts exclusively on L-type Ca channels, the observation that nifedipine predominantly dilates afferent arterioles implicates intrarenal heterogeneity in the distribution of L-type Ca channels and suggests that it potentially causes glomerular hypertension. In contrast, recently developed Ca channel blockers (CCBs), including mibefradil and efonidipine, exert blocking action on L-type and T-type Ca channels and elicit vasodilation of afferent and efferent arterioles, which suggests the ...
This gene encodes the pore-forming alpha subunit of a voltage gated calcium channel. The encoded protein is a member of a subfamily of calcium channels referred to as is a low voltage-activated, T-type, calcium channel. The channel encoded by this protein is characterized by a slower activation and inactivation compared to other T-type calcium channels. This protein may be involved in calcium signaling in neurons. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]
We have recently shown that felodipine, a long-acting dihydropyridine L-type calcium channel blocker (CCB), up-regulates nitric oxide (NO) production and endothelial NO synthase (eNOS) expression and activity in cultured endothelial cells as well as in animals with chronic renal failure. This study was intended to compare the effects of prototypes of the three classes of L-type CCBs on the NO system in cultured human coronary artery endothelial cells. Thus, cultured endothelial cells were incubated either with nifedipine, diltiazem, or verapamil for 24 h at 10−5 to 10−7 M concentrations. Cells incubated with inactive vehicle served as controls. NO production, as discerned from total nitrate plus nitrite recovered in the medium, was significantly increased by nifedipine (P , .03) and by diltiazem (P , .05). However, NO production remained unchanged with verapamil (P = NS). Similarly, eNOS protein abundance was increased significantly by nifedipine (P , .05) and diltiazem (P , .05). In ...
Calcium channel blockers are drugs that block the entry of calcium into the cells of the heart and blood vessels walls by interacting with calcium channels. They are primarily used to treat hypertension, angina and arrhythmias. Learn about the different classes of calcium channel blocker medications and how they are used.
We have found that phospholemman (PLM) associates with and modulates the gating of cardiac L-type calcium channels (Wang et al., Biophys J 98: 1149-1159, 2010). The short 17 amino acid extracellular NH2-terminal domain of PLM contains a highly conserved PFTYD sequence that defines it as a member of the FXYD family of ion transport regulators. Although we have learned a great deal about PLM-dependent changes in calcium channel gating, little is known regarding the molecular mechanisms underlying the observed changes. Therefore, we investigated the role of the PFTYD segment in the modulation of cardiac calcium channels by individually replacing Pro-8, Phe-9, Thr-10, Tyr-11, and Asp-12 with alanine (P8A, F9A, T10A, Y11A, D12A). In addition, Asp-12 was changed to lysine (D12K) and cysteine (D12C). As expected, wild-type PLM significantly slows channel activation and deactivation and enhances voltage-dependent inactivation (VDI). We were surprised to find that amino acid substitutions at Thr-10 and ...
Gomez-Ospina et al. provide evidence for an intriguing mechanism whereby voltage-dependent calcium channels modulate gene transcription. Calcium entry through voltage-gated channels in the plasma membrane provides a link between electrical activity and changes in gene expression. Gomez-Ospina et al. found that, whereas an antibody that recognized the full-length Cav1.2 calcium channel localized to membrane and cytosolic fractions of rat brain cortex, an antibody that recognized the C-terminal fragment, which is proteolytically cleaved, appeared in the nucleus. The C-terminal fragment was abundant in nuclei of GABAergic neurons; moreover, nuclear fluorescence was apparent in neurons or glioblastoma cells expressing a construct in which the Cav1.2 C terminus was fluorescently labeled. Treatments aimed at lowering cytoplasmic calcium increased nuclear abundance of the Cav1.2 fragment, whereas treatments that increase intracellular calcium decreased it. The Cav1.2 fragment immunoprecipitated with ...
The steady‐state gating activity of the InsP3R is biphasically regulated by [Ca2+]i, indicating that the channel also has low‐affinity inhibitory Ca2+ binding sites (Foskett et al, 2007). Ca2+ inhibition can provide a negative feedback mechanism to either terminate or prevent Ca2+ release as the local [Ca2+]i is raised by InsP3R‐mediated Ca2+ release. This can have significant roles in generating Ca2+ spikes and oscillations, and in creating highly localized Ca2+ signals in subcellular compartments by preventing runaway Ca2+ release due to CICR. Switching [Ca2+]i from 2 μM (optimal) to 300 μM (inhibitory; Ionescu et al, 2006) in the presence of 10 μM InsP3 inhibited channel gating (Fig 1K). This shows that InsP3 binding does not render the low‐affinity inhibitory Ca2+ sites inaccessible for Ca2+ binding, disproving previous claims (Adkins & Taylor, 1999). The mean latency for Ca2+ inhibition (290±40 ms, n=186, N=7) was substantially longer than that for Ca2+ activation ...
Our long-standing research program includes the study of cancer and cancer treatment on the musculoskeletal system. Most recently, we have shown that TGF-b, released as a consequence of increased osteoclastic bone resorption [in states of bone metastases as well as non-malignant Camurati-Engelmann Disease (CED)], causes muscle weakness by oxidation of the skeletal muscle calcium channel ryanodine receptor (RYR). Since oxidation of RyR can impair insulin secretion, we want to determine if states of high bone turnover associated with increased systemic TGF-b also result in impaired insulin secretion and altered glucose metabolism. These studies fit in the Cellular and Molecular Metabolism as well as Islet Function and Survival. ...
Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs). The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of ...
Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs). The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of ...
Voltage-gated calcium channels contain a pore-forming alpha1 subunit and auxiliary alpha2delta, beta and gamma subunits. Of the three auxiliary subunits, gamma is least understood. Cardiac myocytes express three gamma isoforms: gamma4, gamma6 and gamma 7. Low-voltage activated (LVA) calcium currents regulate rhythmic activity and cell proliferation in the heart. Previous studies using heterologous expression systems showed that gamma6 robustly inhibits Cav3.1 current, which is a major LVA component in adult atrial myocytes. On the other hand, gamma4 and gamma7 do not inhibit Cav 3.1 currents. Using whole-cell electrophysiology, we demonstrated that gamma 6 also inhibits LVA currents in HL-1 cardiomyocytes, confirming its function in native cells. Previous studies from our lab indicated that the first transmembrane domain of gamma6 is responsible for its inhibitory function. Using mutational analysis, we further identified the first GxxxA motif in the first transmembrane domain of gamma6 as being ...
An input/output data channel operates in conjunction with a virtual memory computer. A channel operation is commenced with the execution of a start I/O instruction which transfers a channel address word (CAW) to the channel. The CAW contains a virtual command address pointing to the beginning of a virtual channel program. The virtual command address is presented to a channel look-aside buffer which translates the virtual command to a real memory address for accessing main storage. The virtual channel command words (CCWs) which comprise the channel program are successively translated by the channel look-aside buffer. A virtual address stack within the buffer holds active virtual data addresses and command addresses for each channel. Interlocking between this stack and a CPU translation mechanism is provided by an I/O bit array. The I/O bit array contains a count mechanism for each memory frame which may be addressed by the channel. Each time a memory frame is addressed by any of the channels, the
DESCRIPTION (provided by applicant): Airway smooth muscle (ASM) remodeling in chronic asthma involves structural and functional changes from healthy into hyper-reactive and proliferative/hypertrophic ASM. ASM remodeling is an important determinant in airway obstruction and decline pulmonary function in asthma that compounds the well- established immune/inflammatory components. These ASM phenotypic changes are of great clinical importance yet remains poorly understood. A more recent concept is that ASM not only contributes to physical obstruction of airways, but acts as immune effector in asthma. Orai1 encodes canonical, ubiquitous and evolutionarily-conserved Ca2+ release-activated Ca2+ (CRAC) channels regulated by the endoplasmic reticulum (ER) Ca2+ sensor STIM1. We showed that CRAC mediate proliferative signals during pathological smooth muscle remodeling. However, Orai1-mediated CRAC is widely functional in most, if not all, tissues rendering its specific targeting for therapy challenging. ...
The ability of an organism to detect injury or potentially harmful thermal, mechanical and chemical stimuli - a process generally referred to as nociception - is crucial for survival. The recent discovery of TRP channels as molecular sensors of multiple noxious stimulus modalities (thermal, mechanical and chemical stimuli) in primary sensory neurons has opened-up new avenues for understanding how organisms monitor their internal and external environment. The first TRP ion channel was identified in a Drosophila melanogaster (a fruit fly) mutant, in which the photoreceptor cells responded with a transient rather than a sustained receptor potential to continuous light. The mutant was therefore named trp. The trp gene encodes a calcium permeable ion channel - the founding member of a large family of cation channels present in worms, insects, fish and mammals. However, the discovery of mammalian thermosensitive TRP ion channels in sensory neurons was triggered by the use of natural products derived from
Null mutants in Ca2+-signaling genes, such as Orai, STIM, and IP3R, have pleiotropic effects during development, which frequently result in either defective development or early lethality of the organism (Venkatesh and Hasan, 1997; Joshi et al., 2004). Consequently, identification of molecular and cellular mechanisms regulated by intracellular Ca2+ signaling and SOCE in differentiated neurons requires genetic tools that can be restricted in their spatiotemporal expression. We addressed this problem by first studying a hypomorphic allele of the single Drosophila Orai gene followed by developing a dominant-negative Orai transgene whose expression could be manipulated in a stage-specific and tissue-specific manner. Temporal expression of the dominant-negative E180A transgene established that SOCE requirement in dopaminergic neurons is during pupal maturation of the flight circuit. Moreover, loss of SOCE does not affect the number of dopaminergic neurons; rather, it alters their transcriptional ...
These toxins target sodium and calcium channels in the body. At the time of their discovery, little was known about voltage-gated calcium-channels, which are present in excitable cells such as muscle cells and neurons and which initiate a response such as contraction or excitation, respectively, upon the passage of calcium through the channels. One of Oliveras peptides from cone snails, the Ω-conotoxin GVIA, functioned through inhibition of calcium uptake through binding to neuronal calcium channels. News of this discovery caused a boon of research in this field, yielding more than 2,000 studies, which utilized Oliveras synthesized version of the Ω-GVIA peptide, active at concentrations of less than 1E-12M! Research in this field finally resulted in the purification of the neuronal calcium channel, which was subsequently named after Oliveras peptide, "the conotoxin receptor." In addition to the impact this discovery had in the field of neuroscience, a conotoxin peptide has been approved as ...
Hi! I was wondering if anyone here has tried a calcium channel blocker before? If so, what calcium channel blocker did you try and did you have any side-effects? Did it help your migraines? I am...
Calcium channel blockers can cause water retention and can make chest pain worse. This portion of the eMedTV Web site describes other important calcium channel blocker warnings and precautions, including who should not take these drugs.
In this study, we identified a novel class of CRAC channel blockers using high-throughput chemical library screen and asked how inhibition of Ca2+ signaling during TCR stimulation influenced differentiation and effector functions of T cells in vitro and in vivo. Using a combination of NFAT translocation as readout and a cell line harboring amplified CRAC currents, we identified a novel class of immunomodulators, compound 5, and its analogs. A more potent analog of the lead compound, compound 5D, blocked CRAC currents generated by WT Orai1 and a constitutively active mutant of Orai1 without affecting Orai1 and STIM1 translocation, indicating that the blocking mechanism directly involves the pore-forming subunit, Orai1. Further studies of CRAC current inhibition showed block by extracellular, but not intracellular, application of compound 5D, suggesting that the binding site is accessible only from the extracellular face of Orai1. Comprehensive mutational analysis of all the residues with possible ...
Calmodulin (CaM) is a ubiquitous calcium-binding protein responsible for the binding and activation of a vast number of enzymes and signaling pathways. It contains two lobes that bind two calcium ions each, separated by a flexible central linker. This structural flexibility allows CaM to bind and regulate a large number of diverse protein targets within the cell in response to Ca2+ gradients. Voltage gated calcium channels (CaVs), as main sources of extracellular Ca2+, are crucial for a number of physiological processes, from muscle contraction to neurotransmission and endocrine function. These large transmembrane proteins open in response to membrane depolarization and allow gated entry of Ca2+ ions into the cytoplasm. Their regulation is currently the subject of intense investigation due to its pharmacological and scientific importance. CaM has been previously shown to pre-associate and act as a potent inhibitor of one class of high-voltage activated (HVA) channels called L-type channels via ...
My research focuses on the involvement of two voltage-gated calcium channel mutations in epilepsy. Epilepsy is a neurological disorder characterized by spontaneous seizures that can cause brain damage. In epilepsy, the normal pattern of neuronal activity becomes disturbed, causing convulsions, muscle spasms, and the loss of consciousness. Epilepsy may develop because of an abnormality in brain wiring, an imbalance in neurotransmitters, changes in ion channels, or some combination of these factors.. Ion channels are cell membrane proteins that allow the passage of ions, such as calcium, into or out of the cell, which generates the electrical signals of neural networks. Voltage-gated calcium channels are a type of ion channel, which allows the passage of calcium ions into the cell. They have a pore through which calcium passes, and one or more auxiliary subunits that regulate pore opening and closing. The auxiliary subunit my research focuses on is the β subunit. The β subunit functions in ...
Neurons fired as the specific calcium channels at play, called L-type voltage-gated calcium channels (LTCCs), boosted the release of a neurotransmitter called GABA.
The task of the intracellular transport machinery is to deliver functional channels at the right place and at the right time. The life of the channel protein starts in the endoplasmic reticulum. Here channels that have approved a quality control begin their intracellular journey to their final destination. For this channels are packed into vesicles that actively navigate through the dense network of actin- and tubulin-based cytoskeleton that serve as tracks for the intracellular trafficking. Mature channels assembled at the plasma membrane are finely regulated for their permeation properties until they are removed from the cell surface by endocytosis. A second quality control may decide their sorting fate after internalization: either the channel is recycled back to the plasma membrane or derived to the degradation pathway ...
Depletion of intracellular Ca2+ stores leads to the activation of Ca2+-permeable channels in the plasma membrane, a reversible process known as store-operated Ca2+ entry (SOCE). The Ca2+ that enters through the store-operated channels can then be pumped into stores within the ER to replenish them. Depleted Ca2+ stores in the ER stimulate the ER Ca2+ sensor Stim1 to rearrange from tubular structures throughout the ER to punctate structures near the plasma membrane, where it activates the SOCE channels. On page 762, James W. Putney, Jr and colleagues investigate the poorly understood mechanism and determinants of the localisation and reversal of Stim1 puncta formation. They show that SOCE is tightly coupled to the formation of Stim1 puncta, because the basis for SOCE termination is the reversal of punctate Stim1 localisation, which, in turn, is dependent on SOCE-dependent store refilling. In addition, they report on the role of the pharmacologic agent ML-9 as a potential antagonist of ...
Here, we report the novel findings that in human adrenal glomerulosa cells both basal and stimulated rates of aldosterone production depend on voltage-gated calcium currents through T-type as well as L-type calcium channels. These findings are surprising because patch-clamp studies consistently report the basal membrane potential of ZG cells to be very hyperpolarized (around −80 mV), a potential at which high threshold L-type calcium channels are not expected to be active. In contrast, low threshold T-type calcium channels are activated at more hyperpolarized potentials and have a permissive window of steady-state activity at more hyperpolarized potentials (Perez-Reyes 2003). When stimulated by low physiological concentrations of Ang II or small increases in extracellular potassium, the membrane potential of ZG cells can rapidly reach the permissive voltage window for persistent T-type, but not L-type, calcium channel activity, that allows steady-state calcium influx (Rossier 2016). Therefore, ...
Cardiac myocytes express two types of voltage operated calcium currents, a high voltage activated (HVA) L-type, and a low voltage activated (LVA) T-type. Influx of calcium into the cell through the L-type channel is responsible for excitation-contraction coupling in the heart. The T-type calcium current has been associated with growth and differentiation in a number of different cell types. An atrial myocyte cell line (HL-1) that selectively expresses T-type calcium current was employed to show that inhibiting calcium influx through the T-type calcium channel inhibits cellular proliferation. Drug dosage studies demonstrate that the T-type calcium channel responsible for this effect is Cav 3.1. Furthermore, blocking the calcium influx through the T-type calcium channel arrests cells in the G2/M phase of the cell cycle. Interestingly, the proliferative effect of calcium influx through the T-type calcium channel appears to happen in the early G1 phase of the cell cycle ...
Looking for online definition of Epithelial calcium channel 2 in the Medical Dictionary? Epithelial calcium channel 2 explanation free. What is Epithelial calcium channel 2? Meaning of Epithelial calcium channel 2 medical term. What does Epithelial calcium channel 2 mean?
Currents flowing through single dihydropyridine-sensitive Ca2+ channels were recorded from cell-attached patches on C2 myotubes. In the presence of dihydropyridine agonist to prolong the duration of single-channel openings, adding micromolar concentrations of lanthanum (La), cerium (Ce), neodymium (Nd), gadolinium (Gd), dysprosium (Dy), or ytterbium (Yb) to patch electrodes containing 110 mM BaCl2 caused the unitary Ba2+ currents to fluctuate between fully open and shut states. The kinetics of channel blockade followed the predictions of a simple open channel block model in which the fluctuations of the single-channel current arose from the entry and exit of blocking ions from the pore. Entry rates for all the lanthanides tested were relatively insensitive to membrane potential, however, exit rates depended strongly on membrane potential increasing approximately e-fold per 23 mV with hyperpolarization. Individual lanthanide ions differed in both the absolute rates of ion entry and exit: entry ...
Dantrolene and nimodipine dramatically reduce the number of activated microglia in the hippocampus and reduce the expression of various pro-inflammatory cytokines. It is not clear from our data whether the anti-inflammatory effects of dantrolene and nimodipine are due to direct action on the microglia themselves or an indirect effect via normalization of neuronal Ca+2 levels. Neurotoxicity of conditioned media from activated microglia is reduced when drugs blocking L-VDCCs or RyRs are applied to the microglia cultures [12-14]. However, the in vivo anti-inflammatory effects of these drugs are not so clear-cut. Following facial nerve transection, nimodipine treatment improves motor neuron survival without reducing microglia activation [53]. However, after ischemic-reperfusion injury, nimodipine does improve behavioral outcomes while concurrently reducing microglia activation [54]. Similarly, in vivo treatment with dantrolene is neuroprotective and improves behavioral outcomes in various in vivo ...
Cyclic nucleotide-gated (CNG)1 ion channels are key players in visual and olfactory signal transduction pathways (reviewed in Lancet, 1986; Yau and Baylor, 1989; Zufall et al., 1994). Although they are only weakly voltage dependent, CNG channels have regions of sequence similarity with voltage-gated channels (Jan and Jan, 1990). One region of high conservation between CNG channels and voltage-gated channels is the P region, thought to line a portion of the ion-conducting pore. Shaker K+ channels that have had portions of their P region replaced with the corresponding region from CNG channels take on many of the permeation properties of CNG channels (Heginbotham et al., 1992). These chimeric channels become permeable to Na+ as well as to K+ and become blocked by the divalent cations Mg2+ and Ca2+. Like voltage-gated channels, CNG channels are thought to possess multi-ion pores (Furman and Tanaka, 1990; Sesti et al., 1995). The external divalent cation binding site is thought to involve the E363 ...
We have tested the periodate-oxidized ATP analogue 2′,3′-dialdehyde adenosine triphosphate (oATP) as a ligand for the skeletal muscle ryanodine receptor/Ca(2+)-release channel. Ca2+ efflux from passively loaded heavy sarcoplasmic reticulum vesicles of skeletal muscle is biphasic. oATP stimulates the initial phase of Ca2+ release in a concentration-dependent manner (EC50 160 microM), and the efflux proceeds with a half-time in the range 100-200 ms. This oATP-modulated initial rapid Ca2+ release was specifically inhibited by millimolar concentrations of Mg2+ and micromolar concentrations of Ruthenium Red, indicating that the effect of oATP was mediated via the ryanodine receptor. The purified Ca(2+)-release channel was incorporated into planar lipid bilayers, and single-channel recordings were carried out to verify a direct interaction of oATP with the ryanodine receptor. Addition of oATP to the cytoplasmic side activated the channel with an EC50 of 76 microM, which is roughly 30-fold higher ...
TY - JOUR. T1 - Nitric oxide-dependent activation of CaMKII increases diastolic sarcoplasmic reticulum calcium release in cardiac myocytes in response to adrenergic stimulation. AU - Curran, Jerry. AU - Tang, Lifei. AU - Roof, Steve R.. AU - Velmurugan, Sathya. AU - Millard, Ashley. AU - Shonts, Stephen. AU - Wang, Honglan. AU - Santiago, Demetrio. AU - Ahmad, Usama. AU - Perryman, Matthew. AU - Bers, Donald M. AU - Mohler, Peter J.. AU - Ziolo, Mark T.. AU - Shannon, Thomas R.. PY - 2014/2/3. Y1 - 2014/2/3. N2 - Spontaneous calcium waves in cardiac myocytes are caused by diastolic sarcoplasmic reticulum release (SR Ca2+ leak) through ryanodine receptors. Beta-adrenergic (β-AR) tone is known to increase this leak through the activation of Ca-calmodulin-dependent protein kinase (CaMKII) and the subsequent phosphorylation of the ryanodine receptor. When b-AR drive is chronic, as observed in heart failure, this CaMKII-dependent effect is exaggerated and becomes potentially arrhythmogenic. Recent ...
This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ... calcium channel activity. • metal ion binding. • voltage-gated ion channel activity. • ion channel activity. • protein binding ... high voltage-gated calcium channel activity. • voltage-gated calcium channel activity involved in AV node cell action potential ... voltage-gated calcium channel activity. • voltage-gated calcium channel activity involved in cardiac muscle cell action ...
ion channel activity. • protein binding. • actin binding. • calcium channel activity. • cation channel activity. • protein ... cation channel complex. Biological process. • regulation of cytosolic calcium ion concentration. • positive regulation of ... store-operated calcium channel activity. • clathrin binding. • inositol 1,4,5 trisphosphate binding. • ... Heiner I, Eisfeld J, Lückhoff A (2004). "Role and regulation of TRP channels in neutrophil granulocytes". Cell Calcium. 33 (5-6 ...
Cl−: Chloride channel. *Calcium-activated chloride channels *Anoctamin *ANO1. *Bestrophin *1. *2 ... gap junction channel activity. Cellular component. • cytoplasm. • integral component of membrane. • gap junction. • cell ... Connexins are membrane-spanning proteins that assemble to form gap junction channels that facilitate the transfer of ions and ... Typically the GJB1 protein forms channels through the myelin to the internal Schwann cell or oligodendrocyte, allowing ...
Cl−: Chloride channel. *Calcium-activated chloride channels *Anoctamin *ANO1. *Bestrophin *1. *2 ... When two identical connexons come together to form a Gap junction channel, it is called a homotypic GJ channel. When one ... Channel composition is thought to influence the function of gap junction channels. ... Properties of connexon channel pairs[edit]. Light microscope images do not allow us to see connexons themselves but do let us ...
channel regulator activity. • calcium channel activity. • voltage-gated calcium channel activity. • calcium channel regulator ... Voltage-dependent calcium channel gamma-4 subunit is a protein that in humans is encoded by the CACNG4 gene.[5][6] ... CACNG4, calcium voltage-gated channel auxiliary subunit gamma 4. External IDs. OMIM: 606404 MGI: 1859167 HomoloGene: 8674 ... voltage-gated calcium channel complex. • integral component of membrane. • integral component of plasma membrane. • AMPA ...
ion channel activity. • store-operated calcium channel activity. • protein binding. • calcium channel activity. • clathrin ... regulation of cytosolic calcium ion concentration. • calcium ion transmembrane transport. • calcium ion transport. • nervous ... calcium channel complex. • membrane. • cytoplasm. • growth cone. • neuronal cell body. • dendrite. • membrane raft. • cation ... Beech DJ (2007). "Bipolar phospholipid sensing by TRPC5 calcium channel". Biochem. Soc. Trans. 35 (Pt 1): 101-4. doi:10.1042/ ...
"Functional coupling of intracellular calcium and inactivation of voltage-gated Kv1.1/Kvbeta1.1 A-type K+ channels". Proc. Natl ... channel), voltage gated potassium channel HBK1, voltage gated potassium channel subunit Kv1.1, voltage-gated K+ channel HuKI ... potassium channel activity. • delayed rectifier potassium channel activity. • voltage-gated ion channel activity. • GO:0015388 ... Potassium voltage-gated channel subfamily A member 1 also known as Kv1.1 is a shaker related voltage-gated potassium channel ...
calcium channel activity. • metal ion binding. • voltage-gated ion channel activity. • voltage-gated calcium channel activity. ... a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell ... Voltage-dependent calcium channel subunit alpha2delta-2 is a protein that in humans is encoded by the CACNA2D2 gene.[5] ... CACNA2D2, CACNA2D, calcium voltage-gated channel auxiliary subunit alpha2delta 2. External IDs. OMIM: 607082 MGI: 1929813 ...
... is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group.[1] It is also known to ... Cinnarizine is classified as a selective antagonist of T-type voltage-operated calcium ion channels, because its binding blocks ... due to calcium channel blockade), which happen mostly in brain and the fact that it is also used as a labyrinthine sedative.[15 ... and it has been shown that this drug preferentially binds to its target calcium channels when they are in an open, as opposed ...
Calcium channel. Voltage-gated. *CACNA1A *Familial hemiplegic migraine 1. *Episodic ataxia 2 ...
The main ones are the L-type calcium channel α1-subunit[1] and potassium inward rectifier 2.6;[3] it is therefore classified as ... Genetic mutations in the L-type calcium channel α1-subunit (Cav1.1) have been described in Southern Chinese with TPP. The ... The condition has been linked with genetic mutations in genes that code for certain ion channels that transport electrolytes ( ... Furthermore, mutations have been reported in the genes coding for potassium voltage-gated channel, Shaw-related subfamily, ...
Calcium channel. Voltage-gated. *CACNA1A *Familial hemiplegic migraine 1. *Episodic ataxia 2 ...
Most frequent side effects are nausea, orthostatic hypotension, headaches, and vomiting through stimulation of the brainstem vomiting centre.[9] Vasospasms with serious consequences such as myocardial infarction and stroke that have been reported in connection with the puerperium, appear to be extremely rare events.[10] Peripheral vasospasm (of the fingers or toes) can cause Raynaud's Phenomenon. Bromocriptine use has been anecdotally associated with causing or worsening psychotic symptoms (its mechanism is in opposition of most antipsychotics, whose mechanisms generally block dopamine).[11] Pulmonary fibrosis has been reported when bromocriptine was used in high doses for the treatment of Parkinson's disease.[12] Use to suppress milk production after childbirth was reviewed in 2014 and it was concluded that in this context a causal association with serious cardiovascular, neurological or psychiatric events could not be excluded with an overall incidence rate estimated to range between 0.005% ...
InChI=1S/C25H29N3O2/c1-27-14-18(13-26-25(29)30-16-17-7-4-3-5-8-17)11-21-20-9-6-10-22-24(20)19(12-23(21)27)15-28(22)2/h3-10,15,18,21,23H,11-14,16H2,1-2H3,(H,26,29)/t18-,21+,23+/m0/s1 ...
Calcium channel. 7. Exocytosis of a vesicle. 8. Recaptured neurotransmitter. ... Amino acid neurotransmitter release (exocytosis) is dependent upon calcium Ca2+ and is a presynaptic response. There are ...
Calcium sulfate. Strontium sulfate. Barium sulfate Except where otherwise noted, data are given for materials in their standard ... Channel blockers. class I. (Na+ channel blockers). class Ia (Phase 0→ and Phase 3→). *Ajmaline ... Other inorganic sulfate salts such as sodium sulfate and calcium sulfate may be used in the same way. ... In a magnesium-deficient marine aquarium, calcium and alkalinity concentrations are very difficult to control because not ...
The resultant products bind to inositol triphosphate (IP3) receptors through calcium ion channels. The calcium comes from ... They can also block calcium ion channels to hyperpolarize postsynaptic cells. Significance[edit]. There are many applications ... DSIs can be blocked by ionotropic receptor calcium ion channel antagonists on the somata and proximal apical dendrites of CA1 ... These depolarizations activate voltage-dependent calcium channels. They later become hyperpolarizing as the mammal matures. To ...
N-type calcium-channel blocker.. Intrathecal.. Protein binding = 50%; half-life = 2.9-6.5 hours; excretion = urine (,1%).[122] ... Binds to the α2δ-1 subunit of voltage gated calcium ion channels in the spinal cord. May also modulate NMDA receptors and ... Comes in calcium salt form; fairly soluble in water.. Is metabolised to aspirin and urea. As per aspirin.. Oral.. No data.. ... Comes in free form and calcium salt; acetic acid derivative.. As per diclofenac.. PO.. No data.. As per diclofenac.. As per ...
Different calcium channels are present in vascular tissue and cardiac tissue; an in vitro study on human vascular and cardiac ... Felodipine is a calcium channel blocker. Felodipine has additionally been found to act as an antagonist of the ... Felodipine is a medication of the calcium channel blocker type which is used to treat high blood pressure. Felodipine is used ... Felodipine is a member of the 1,4-dihydropyridine class of calcium channel blockers. It is a racemic mixture, and is insoluble ...
Calcium channel blockersEdit. Concurrent therapy with calcium channel blocker may increase risk of low blood pressure, kidney ... "Calcium-channel blocker-clarithromycin drug interactions and acute kidney injury". JAMA. 310 (23): 2544-2553. doi:10.1001/jama. ... compared to pairing calcium channel blockers with azithromycin, a drug similar to clarithromycin but without CYP3A4 inhibition. ...
"Neuroleptics of the diphenylbutylpiperidine series are potent calcium channel inhibitors". Proceedings of the National Academy ... Relationship with receptors for 1,4-dihydropyridines and phenylalkylamines and with Ca2+ channel blockade". European Journal of ...
Cheng, R. C., Tikhonov, D. B., & Zhorov, B. S. (2009). Structural model for phenylalkylamine binding to L-type calcium channels ... BRL-32872's class III activity is directed towards the human ether-a-go-go-related gene (hERG) K+ channel.[4] hERG channels are ... 1995). Electrophysiological effect of BRL-32872, a novel antiarrhythmic agent with potassium and calcium channel blocking ... BRL-32872 binds with high affinity to open hERG channels, and inhibits the rapidly activating component of the IK.[4] BRL-32872 ...
"Calcium block of Na+ channels and its effect on closing rate". Proceedings of the National Academy of Sciences of the United ... The skeleton acts as an extremely large calcium store (about 1 kg) compared with the plasma calcium store (about 180 mg). ... releases free calcium ions into the plasma ionized calcium pool. PTH has a second action on the kidneys. It stimulates the ... The plasma ionized calcium (Ca2+) concentration is very tightly controlled by a pair of homeostatic mechanisms.[49] The sensor ...
... the action potential activates calcium channels (VDCCs) that cause a local influx of calcium. The increase in calcium is ... Voltage-dependent calcium channel (VDCC) Allows the rapid influx of calcium during an action potential. ... The arrival of an action potential opens voltage gated calcium channels near the SNARE/complexin complex. Calcium then binds to ... Stanley EF (1993). "Single calcium channels and acetylcholine release at a presynaptic nerve terminal". Neuron. 11 (6): 1007- ...
Medical treatment - drugs (e.g., cholesterol lowering medications, beta-blockers, nitroglycerin, calcium channel blockers, etc ... Calcium phosphate (hydroxyapatite) deposits in the muscular layer of the blood vessels appear to play a significant role in ... Plaques can be thought of as large "pimples" that protrude into the channel of an artery, causing a partial obstruction to ... With atherosclerosis, the artery's lining becomes hardened, stiffened, and accumulates deposits of calcium, fatty lipids, and ...
Calcium channel blockers *Verapamil. *Hormones *Estrogens. *TRH. Physiological causesEdit. Physiological (i.e., non- ...
With the emergence of two-photon microscopy and calcium imaging, we now have powerful experimental methods with which to test ... Voltage sensitive ion channels are glycoprotein molecules which extend through the lipid bilayer, allowing ions to traverse ... "Intracellular Calcium Dynamics Permit a Purkinje Neuron Model to Perform Toggle and Gain Computations Upon its Inputs" ... "Intracellular Calcium Dynamics Permit a Purkinje Neuron Model to Perform Toggle and Gain Computations Upon its Inputs" ...
"Direct binding of G-protein betagamma complex to voltage-dependent calcium channels". Nature. 385 (6615): 446-50. doi:10.1038/ ... Wnt signaling pathway, calcium modulating pathway. • protein folding. • G-protein coupled receptor signaling pathway. ... positive regulation of cytosolic calcium ion concentration. • cellular response to glucagon stimulus. • cellular response to ... of gbetagamma with a C-terminal gbetagamma-binding domain of the Ca2+ channel alpha1 subunit is responsible for channel ...
Term: small/intermediate conductance calcium-activated potassium channel protein. ID: PIRSF038511 Mouse Protein Superfamily ...
Second, if calcium entry through N-type calcium channels is prevented, the delayed generation of damage is prevented. ... that neuroprotection by selective N-type calcium channel antagonists is mediated directly through neuronal calcium channels. In ... Pharmacological characterisation of the calcium channels coupled to the plateau phase of KCl-induced free calcium elevated in ... which blocks N-type and other presynaptic neuronal calcium channels. The dihydropyridine nifedipine and the mixed calcium ...
The intermediate conductance calcium-activated potassium channel KCa3.1 (also known as KCNN4 and IKCa), a member of the calcium ... Keywords: Atherosclerosis, Calcium, Calcium Signaling, Cell Proliferation, Potassium Channels, Vascular Biology, Vascular ... calcium-activated potassium channel. CREB. cAMP-response element-binding protein. CsA. cyclosporin A. EBIO. 1-ethyl-2- ... The intermediate conductance calcium-activated potassium channel KCa3.1 contributes to a variety of cell activation processes ...
The large-conductance calcium-activated potassium channels (BKCa) and voltage-gated sodium channels were expressed in cortical ... In single-channel recordings, open probability (N · Po) and single-channel conductance for BKCa channels were determined by all ... roles of large conductance calcium-activated potassium channels and voltage-gated sodium channels. ... BKCa channels also play an important role in seizure etiology. Loss-of-function BKCa channel mutations can lead to temporal ...
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 ... abstract = "To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 2-hydroxy-3- ...
Amlodipine Besylate is a calcium channel blocker drug. It relaxes blood vessels so blood can flow easily. It is also used to ...
Calcium Channel Blockers (Mayo Foundation for Medical Education and Research) Also in Spanish ... Calcium Supplements: Do They Interfere with Blood Pressure Drugs? (Mayo Foundation for Medical Education and Research) Also in ...
Taking a calcium supplement of up to 1,000 mg per day can help women live longer, according to a study whose lead author was ... Calcium supplements linked to longer lifespans in women Published: 22May2013 ... McGill research team studies how calcium compounds accumulate in the arteries Published: 31Jan2018 ... UAlberta and McGill scientists uncover a hidden calcium cholesterol connection Published: 27Jul2017 ...
... opening of the L-type calcium channel permits influx of calcium into the cell. The calcium binds to the calcium release ... High-voltage-gated calcium channels include the neural N-type channel blocked by ω-conotoxinGVIA, the R-type channel (R stands ... Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ... In skeletal muscle, the actual opening of the channel, which is mechanically gated to a calcium-release channel (a.k.a. ...
P-type calcium channel ("Purkinje") /Q-type calcium channel. HVA (high voltage activated). Cav2.1 (CACNA1A). α2δ, β, possibly γ ... Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ... opening of the L-type calcium channel permits influx of calcium into the cell. The calcium binds to the calcium release ... High-voltage-gated calcium channels include the neural N-type channel blocked by ω-conotoxin GVIA, the R-type channel (R stands ...
Calcium permeability of ligand-gated channels.. Burnashev N1.. Author information. 1. Max-Planck-Institut für medizinische ... Ligand-gated channels activated by excitatory neurotransmitters: glutamate, acetylcholine, ATP or serotonin are cation channels ... The functional role of the Ca2+ entry mediated by various ligand-gated channels in mammalian central nervous system is less ... Many of them have different Ca2+ permeability providing immense diversity in Ca2+ entry mediated by ligand-gated channels ...
Single channel studies have identified two types of calcium-activated potassium channel which can also be separated on ... In neurons, these currents are largely activated following calcium influx via voltage gated calcium channels active during the ... It is now clear that BK channels underlie I(c) whereas SK channels underlie I(AHP). The identity of the channels underlying I( ... Channels underlying neuronal calcium-activated potassium currents.. Sah P1, Faber ES. ...
they block the small pores in cells that let calcium pass through, and widen blood vessels as well as affect the activity o ... What are calcium channel blockers?. NEXT QUESTION: Which calcium channel blockers have been studied to treat bipolar disorder? ... How do calcium channel blockers work?. ANSWER These drugs are usually used to treat high blood pressure or heart problems. They ... So calcium channel blockers have been studied as a treatment for bipolar disorder, but there isnt enough evidence yet that ...
They prevent the calcium ions needed for muscle contraction from entering the cells of smooth and cardiac muscle. This causes ... calcium-channel blocker calcium-channel blocker. calcium-channel blocker, any of a class of drugs used in treating hypertension ... Cardizem (diltiazem) is a common calcium-channel blocker. The Columbia Electronic Encyclopedia, 6th ed. Copyright © 2012, ... Some calcium-channel blockers, such as Procardia (nifedipine), slow the electrical impulses that run through heart muscle, thus ...
... also called calcium antagonists, are a newer category of medications which are used to treat heart disease and hypertension. ... Calcium channel blockers, also called calcium antagonists, are a newer category of medications which are used to treat heart ... the calcium channel. The more calcium that gets through the door before the electrical signal comes, the more strongly the ... Calcium channel blockers, like verapamil and its cousins, do not quite lock the revolving door, but they significantly slow ...
Calcium-channel blockers are a type of medicine used to treat high blood pressure and heart rhythm disturbances. They are one ... The specific ingredients in each type of calcium-channel blocker vary. However, the main ingredient is called a calcium-channel ... Calcium-channel blockers are a type of medicine used to treat high blood pressure and heart rhythm disturbances. They are one ... Calcium channel blockers. In: Aronson JK, ed. Meylers Side Effects of Drugs. 16th ed. Waltham, MA: Elsevier; 2016:23-39. ...
A type of blood pressure lowering medication, called a calcium-channel blocker, may be linked with an increased risk of a type ... Atomic level analysis reveals how two classes of calcium channel blockers produce different effects An atomic level analysis ... Tau Therapeutics presents data of T-type calcium channel inhibitors in treatment of pancreatic cancer Tau Therapeutics LLC ... Two-drug combinations containing calcium channel blocker significantly lowers BP In the largest randomized controlled trial of ...
... it acts by selectively blocking the uptake of calcium by the cells.. ... a calcium-channel blocker is a drug that reduces spasm of the blood vessels, lowers blood pressure, and controls angina; ... What is the definition of calcium-channel blocker?. ANSWER A calcium-channel blocker is a drug that reduces spasm of the blood ... vessels, lowers blood pressure, and controls angina; it acts by selectively blocking the uptake of calcium by the cells. ...
... what calcium channel blocker did you try and did you have any side-effects? Did it help your migraines? I am... ... I was wondering if anyone here has tried a calcium channel blocker before? If so, ... I was wondering if anyone here has tried a calcium channel blocker before? If so, what calcium channel blocker did you try and ... I hope the Calcium Channel Blockers work for you! I dont think the Beta Blocker is working for me either at this point (we ...
Calcium channel blockers are used to treat high blood pressure. Theyre as effective as ACE inhibitors in reducing blood ... How calcium channel blockers work. CCBs reduce blood pressure by limiting the amount of calcium or the rate at which calcium ... What are calcium channel blockers?. Calcium channel blockers (CCBs) are a class of medications used to treat high blood ... Natural calcium channel blockers. Magnesium is an example of a nutrient that acts as a natural CCB. Research has shown that ...
Calcium channel blocking agents and the heart. Br Med J (Clin Res Ed) 1985; 291 :1150 ... Calcium channel blocking agents and the heart.. Br Med J (Clin Res Ed) 1985; 291 doi: https://doi.org/10.1136/bmj.291.6503.1150 ...
Channels were inhibited by verapamil and lanthanum. These channels could participate in the regulation of cytoplasmic Ca2+ by ... Free calcium (Ca2+) in the cytoplasm of plant cells is important for the regulation of many cellular processes and the ... The patch-clamp technique was used to study Ca2+ channels in the vacuole of sugar beet cells. Vacuolar currents showed inward ... Control of cytoplasmic Ca2+ involves the activity of pumps, carriers, and possibly ion channels. ...
... Jason Kennerly jkenner at cello.gina.calstate.edu Fri Sep 1 20:06:46 EST 1995 *Previous ...
P-type calcium channel ("Purkinje") /Q-type calcium channel. HVA (high voltage activated). Cav2.1 (CACNA1A). α2δ, β, possibly γ ... "calcium channel" at Dorlands Medical Dictionary *^ Striggow F, Ehrlich BE (August 1996). "Ligand-gated calcium channels inside ... A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous as voltage- ... Calcium Induced Calcium Release - CICR). RYR1, RYR2, RYR3. ER/SR. Calcium-induced calcium release in myocytes[4]. ...
Calcium channel blockers and cancer. . . and other stories BMJ 2018; 361 :k2529 ... There has been some anxiety that calcium channel blockers might encourage growth of malignant cells by reducing intracellular ... mortality from breast cancer was no higher in women who had taken calcium channel blockers than in women who had never used ... Calcium channel blockers and cancer. . . and other stories. BMJ 2018; 361 doi: https://doi.org/10.1136/bmj.k2529 (Published 14 ...
  • Moreover, the effects of resveratrol on action potential firing rate and the BK Ca channel inhibitor TEA (or paxilline)-induced hyperexcitability were also evaluated. (biomedcentral.com)
  • 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)
  • Resveratrol concentration-dependently increased the current amplitude and the opening activity of BK Ca channels, but suppressed the amplitude of voltage-gated sodium currents. (biomedcentral.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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