Potassium Channels: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.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.Potassium Channels, Inwardly Rectifying: Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.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.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.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.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.Kv1.3 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.Kv1.2 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.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.Kv1.1 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.Potassium Channels, Calcium-Activated: Potassium channels whose activation is dependent on intracellular calcium concentrations.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.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.Shaw Potassium Channels: A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.KCNQ1 Potassium Channel: A voltage-gated potassium channel that is expressed primarily in the HEART.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.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.Kv1.4 Potassium Channel: A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.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.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.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.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.Potassium Channels, Tandem Pore Domain: Potassium channels that contain two pores in tandem. They are responsible for baseline or leak currents and may be the most numerous of all K channels.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.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.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).Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.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.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.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.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.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.Chloride Channels: Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.Tetraethylammonium: A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.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).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.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.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.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.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.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.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.Cromakalim: A potassium-channel opening vasodilator that has been investigated in the management of hypertension. It has also been tried in patients with asthma. (Martindale, The Extra Pharmacopoeia, 30th ed, p352)Pinacidil: A guanidine that opens POTASSIUM CHANNELS producing direct peripheral vasodilatation of the ARTERIOLES. It reduces BLOOD PRESSURE and peripheral resistance and produces fluid retention. (Martindale The Extra Pharmacopoeia, 31st ed)Charybdotoxin: A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.Potassium, Dietary: Potassium or potassium compounds used in foods or as foods.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.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.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.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.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.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.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.Tetraethylammonium CompoundsAdenosine 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.Barium Compounds: Inorganic compounds that contain barium as an integral part of the molecule.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Potassium Deficiency: A condition due to decreased dietary intake of potassium, as in starvation or failure to administer in intravenous solutions, or to gastrointestinal loss in diarrhea, chronic laxative abuse, vomiting, gastric suction, or bowel diversion. Severe potassium deficiency may produce muscular weakness and lead to paralysis and respiratory failure. Muscular malfunction may result in hypoventilation, paralytic ileus, hypotension, muscle twitches, tetany, and rhabomyolysis. Nephropathy from potassium deficit impairs the concentrating mechanism, producing POLYURIA and decreased maximal urinary concentrating ability with secondary POLYDIPSIA. (Merck Manual, 16th ed)Kinetics: The rate dynamics in chemical or physical systems.Potassium Compounds: Inorganic compounds that contain potassium as an integral part of the molecule.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.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.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.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.Benzopyrans: Compounds with a core of fused benzo-pyran rings.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.Large-Conductance Calcium-Activated Potassium Channel beta Subunits: The regulatory subunits of large-conductance calcium-activated potassium channels.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.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.Nicorandil: A derivative of the NIACINAMIDE that is structurally combined with an organic nitrate. It is a potassium-channel opener that causes vasodilatation of arterioles and large coronary arteries. Its nitrate-like properties produce venous vasodilation through stimulation of guanylate cyclase.Cesium: A member of the alkali metals. It has an atomic symbol Cs, atomic number 50, and atomic weight 132.91. Cesium has many industrial applications, including the construction of atomic clocks based on its atomic vibrational frequency.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.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.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.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.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.Diazoxide: A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.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.Elapid Venoms: Venoms from snakes of the family Elapidae, including cobras, kraits, mambas, coral, tiger, and Australian snakes. The venoms contain polypeptide toxins of various kinds, cytolytic, hemolytic, and neurotoxic factors, but fewer enzymes than viper or crotalid venoms. Many of the toxins have been characterized.Potassium Isotopes: Stable potassium atoms that have the same atomic number as the element potassium, but differ in atomic weight. K-41 is a stable potassium isotope.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.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.Decanoic Acids: 10-carbon saturated monocarboxylic acids.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.Hydroxy Acids: Organic compounds containing both the hydroxyl and carboxyl radicals.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Kv1.6 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that has been described in NEURONS and ASTROCYTES.Rubidium: An element that is an alkali metal. It has an atomic symbol Rb, atomic number 37, and atomic weight 85.47. It is used as a chemical reagent and in the manufacture of photoelectric cells.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.Potassium Radioisotopes: Unstable isotopes of potassium that decay or disintegrate emitting radiation. K atoms with atomic weights 37, 38, 40, and 42-45 are radioactive potassium isotopes.PhenylenediaminesChlorides: Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.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.Kv Channel-Interacting Proteins: A family of neuronal calcium-sensor proteins that interact with and regulate potassium channels, type A.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Scorpions: Arthropods of the order Scorpiones, of which 1500 to 2000 species have been described. The most common live in tropical or subtropical areas. They are nocturnal and feed principally on insects and other arthropods. They are large arachnids but do not attack man spontaneously. They have a venomous sting. Their medical significance varies considerably and is dependent on their habits and venom potency rather than on their size. At most, the sting is equivalent to that of a hornet but certain species possess a highly toxic venom potentially fatal to humans. (From Dorland, 27th ed; Smith, Insects and Other Arthropods of Medical Importance, 1973, p417; Barnes, Invertebrate Zoology, 5th ed, p503)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.Streptomyces lividans: An actinomycete used for production of commercial ANTIBIOTICS and as a host for gene cloning.Long QT Syndrome: A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.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.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.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)HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Aminopyridines: Pyridines substituted in any position with an amino group. May be hydrogenated, but must retain at least one double bond.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Calcium Channels, P-Type: CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.Picolines: A group of compounds that are monomethyl derivatives of pyridines. (From Dorland, 28th ed)Minoxidil: A potent direct-acting peripheral vasodilator (VASODILATOR AGENTS) that reduces peripheral resistance and produces a fall in BLOOD PRESSURE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p371)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).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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Decapodiformes: A superorder of CEPHALOPODS comprised of squid, cuttlefish, and their relatives. Their distinguishing feature is the modification of their fourth pair of arms into tentacles, resulting in 10 limbs.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.Cation Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of positively charged molecules (cations) across a biological membrane.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Cations: Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.Hypokalemia: Abnormally low potassium concentration in the blood. It may result from potassium loss by renal secretion or by the gastrointestinal route, as by vomiting or diarrhea. It may be manifested clinically by neuromuscular disorders ranging from weakness to paralysis, by electrocardiographic abnormalities (depression of the T wave and elevation of the U wave), by renal disease, and by gastrointestinal disorders. (Dorland, 27th ed)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.Potassium Iodide: An inorganic compound that is used as a source of iodine in thyrotoxic crisis and in the preparation of thyrotoxic patients for thyroidectomy. (From Dorland, 27th ed)ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.Heart: The hollow, muscular organ that maintains the circulation of the blood.Biophysics: The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.RNA, Complementary: Synthetic transcripts of a specific DNA molecule or fragment, made by an in vitro transcription system. This cRNA can be labeled with radioactive uracil and then used as a probe. (King & Stansfield, A Dictionary of Genetics, 4th ed)Quinidine: An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.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.Calcium Channels, Q-Type: CALCIUM CHANNELS located in the neurons of the brain.Anti-Arrhythmia Agents: Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.Tolbutamide: A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)Cnidarian Venoms: Venoms from jellyfish; CORALS; SEA ANEMONES; etc. They contain hemo-, cardio-, dermo- , and neuro-toxic substances and probably ENZYMES. They include palytoxin, sarcophine, and anthopleurine.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.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.Quaternary Ammonium Compounds: Derivatives of ammonium compounds, NH4+ Y-, in which all four of the hydrogens bonded to nitrogen have been replaced with hydrocarbyl groups. These are distinguished from IMINES which are RN=CR2.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.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.Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.Rubidium Radioisotopes: Unstable isotopes of rubidium that decay or disintegrate emitting radiation. Rb atoms with atomic weights 79-84, and 86-95 are radioactive rubidium isotopes.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.Cricetulus: A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.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.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.Nerve Tissue ProteinsBiophysical Phenomena: The physical characteristics and processes of biological systems.Cations, Monovalent: Positively charged atoms, radicals or group of atoms with a valence of plus 1, which travel to the cathode or negative pole during electrolysis.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.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.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Potassium Citrate: A powder that dissolves in water, which is administered orally, and is used as a diuretic, expectorant, systemic alkalizer, and electrolyte replenisher.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.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.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)Calcium Channels, R-Type: CALCIUM CHANNELS located in the neurons of the brain. They are inhibited by the marine snail toxin, omega conotoxin MVIIC.Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.Guanidines: A family of iminourea derivatives. The parent compound has been isolated from mushrooms, corn germ, rice hulls, mussels, earthworms, and turnip juice. Derivatives may have antiviral and antifungal properties.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Isaacs Syndrome: A rare neuromuscular disorder with onset usually in late childhood or early adulthood, characterized by intermittent or continuous widespread involuntary muscle contractions; FASCICULATION; hyporeflexia; MUSCLE CRAMP; MUSCLE WEAKNESS; HYPERHIDROSIS; TACHYCARDIA; and MYOKYMIA. Involvement of pharyngeal or laryngeal muscles may interfere with speech and breathing. The continuous motor activity persists during sleep and general anesthesia (distinguishing this condition from STIFF-PERSON SYNDROME). Familial and acquired (primarily autoimmune) forms have been reported. (From Ann NY Acad Sci 1998 May 13;841:482-496; Adams et al., Principles of Neurology, 6th ed, p1491)Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Myocytes, Cardiac: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).Hyperkalemia: Abnormally high potassium concentration in the blood, most often due to defective renal excretion. It is characterized clinically by electrocardiographic abnormalities (elevated T waves and depressed P waves, and eventually by atrial asystole). In severe cases, weakness and flaccid paralysis may occur. (Dorland, 27th ed)Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.Limbic Encephalitis: A paraneoplastic syndrome marked by degeneration of neurons in the LIMBIC SYSTEM. Clinical features include HALLUCINATIONS, loss of EPISODIC MEMORY; ANOSMIA; AGEUSIA; TEMPORAL LOBE EPILEPSY; DEMENTIA; and affective disturbance (depression). Circulating anti-neuronal antibodies (e.g., anti-Hu; anti-Yo; anti-Ri; and anti-Ma2) and small cell lung carcinomas or testicular carcinoma are frequently associated with this syndrome.Dihydropyridines: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.Sulfonylurea CompoundsSarcolemma: The excitable plasma membrane of a muscle cell. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Acetylcholine: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.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.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.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.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.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Permeability: Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.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)Potassium Permanganate: Permanganic acid (HMnO4), potassium salt. A highly oxidative, water-soluble compound with purple crystals, and a sweet taste. (From McGraw-Hill Dictionary of Scientific and Technical Information, 4th ed)Channelopathies: A variety of neuromuscular conditions resulting from MUTATIONS in ION CHANNELS manifesting as episodes of EPILEPSY; HEADACHE DISORDERS; and DYSKINESIAS.Gramicidin: A group of peptide antibiotics from BACILLUS brevis. Gramicidin C or S is a cyclic, ten-amino acid polypeptide and gramicidins A, B, D are linear. Gramicidin is one of the two principal components of TYROTHRICIN.Epilepsy, Benign Neonatal: A condition marked by recurrent seizures that occur during the first 4-6 weeks of life despite an otherwise benign neonatal course. Autosomal dominant familial and sporadic forms have been identified. Seizures generally consist of brief episodes of tonic posturing and other movements, apnea, eye deviations, and blood pressure fluctuations. These tend to remit after the 6th week of life. The risk of developing epilepsy at an older age is moderately increased in the familial form of this disorder. (Neurologia 1996 Feb;11(2):51-5)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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Pyrroles: Azoles of one NITROGEN and two double bonds that have aromatic chemical properties.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.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.Phosphatidylinositol 4,5-Diphosphate: A phosphoinositide present in all eukaryotic cells, particularly in the plasma membrane. It is the major substrate for receptor-stimulated phosphoinositidase C, with the consequent formation of inositol 1,4,5-triphosphate and diacylglycerol, and probably also for receptor-stimulated inositol phospholipid 3-kinase. (Kendrew, The Encyclopedia of Molecular Biology, 1994)

Leptin suppression of insulin secretion and gene expression in human pancreatic islets: implications for the development of adipogenic diabetes mellitus. (1/9961)

Previously we demonstrated the expression of the long form of the leptin receptor in rodent pancreatic beta-cells and an inhibition of insulin secretion by leptin via activation of ATP-sensitive potassium channels. Here we examine pancreatic islets isolated from pancreata of human donors for their responses to leptin. The presence of leptin receptors on islet beta-cells was demonstrated by double fluorescence confocal microscopy after binding of a fluorescent derivative of human leptin (Cy3-leptin). Leptin (6.25 nM) suppressed insulin secretion of normal islets by 20% at 5.6 mM glucose. Intracellular calcium responses to 16.7 mM glucose were rapidly reduced by leptin. Proinsulin messenger ribonucleic acid expression in islets was inhibited by leptin at 11.1 mM, but not at 5.6 mM glucose. Leptin also reduced proinsulin messenger ribonucleic acid levels that were increased in islets by treatment with 10 nM glucagon-like peptide-1 in the presence of either 5.6 or 11.1 mM glucose. These findings demonstrate direct suppressive effects of leptin on insulin-producing beta-cells in human islets at the levels of both stimulus-secretion coupling and gene expression. The findings also further indicate the existence of an adipoinsular axis in humans in which insulin stimulates leptin production in adipocytes and leptin inhibits the production of insulin in beta-cells. We suggest that dysregulation of the adipoinsular axis in obese individuals due to defective leptin reception by beta-cells may result in chronic hyperinsulinemia and may contribute to the pathogenesis of adipogenic diabetes.  (+info)

Alternative sulfonylurea receptor expression defines metabolic sensitivity of K-ATP channels in dopaminergic midbrain neurons. (2/9961)

ATP-sensitive potassium (K-ATP) channels couple the metabolic state to cellular excitability in various tissues. Several isoforms of the K-ATP channel subunits, the sulfonylurea receptor (SUR) and inwardly rectifying K channel (Kir6.X), have been cloned, but the molecular composition and functional diversity of native neuronal K-ATP channels remain unresolved. We combined functional analysis of K-ATP channels with expression profiling of K-ATP subunits at the level of single substantia nigra (SN) neurons in mouse brain slices using an RT-multiplex PCR protocol. In contrast to GABAergic neurons, single dopaminergic SN neurons displayed alternative co-expression of either SUR1, SUR2B or both SUR isoforms with Kir6.2. Dopaminergic SN neurons expressed alternative K-ATP channel species distinguished by significant differences in sulfonylurea affinity and metabolic sensitivity. In single dopaminergic SN neurons, co-expression of SUR1 + Kir6.2, but not of SUR2B + Kir6.2, correlated with functional K-ATP channels highly sensitive to metabolic inhibition. In contrast to wild-type, surviving dopaminergic SN neurons of homozygous weaver mouse exclusively expressed SUR1 + Kir6.2 during the active period of dopaminergic neurodegeneration. Therefore, alternative expression of K-ATP channel subunits defines the differential response to metabolic stress and constitutes a novel candidate mechanism for the differential vulnerability of dopaminergic neurons in response to respiratory chain dysfunction in Parkinson's disease.  (+info)

Inward rectification in KATP channels: a pH switch in the pore. (3/9961)

Inward-rectifier potassium channels (Kir channels) stabilize the resting membrane potential and set a threshold for excitation in many types of cell. This function arises from voltage-dependent rectification of these channels due to blockage by intracellular polyamines. In all Kir channels studied to date, the voltage-dependence of rectification is either strong or weak. Here we show that in cardiac as well as in cloned KATP channels (Kir6.2 + sulfonylurea receptor) polyamine-mediated rectification is not fixed but changes with intracellular pH in the physiological range: inward-rectification is prominent at basic pH, while at acidic pH rectification is very weak. The pH-dependence of polyamine block is specific for KATP as shown in experiments with other Kir channels. Systematic mutagenesis revealed a titratable C-terminal histidine residue (H216) in Kir6.2 to be the structural determinant, and electrostatic interaction between this residue and polyamines was shown to be the molecular mechanism underlying pH-dependent rectification. This pH-dependent block of KATP channels may represent a novel and direct link between excitation and intracellular pH.  (+info)

Cloning and characterization of the promoters of the maxiK channel alpha and beta subunits. (4/9961)

Large conductance, calcium-activated potassium (maxiK) channels are expressed in nerve, muscle, and other cell types and are important determinants of smooth muscle tone. To determine the mechanisms involved in the transcriptional regulation of maxiK channels, we characterized the promoter regions of the pore forming (alpha) and regulatory (beta) subunits of the human channel complex. Maximum promoter activity (up to 12.3-fold over control) occurred between nucleotides -567 and -220 for the alpha subunit (hSlo) gene. The minimal promoter is GC-rich with 5 Sp-1 binding sites and several TCC repeats. Other transcription factor-binding motifs, including c/EBP, NF-kB, PU.1, PEA-3, Myo-D, and E2A, were observed in the 5'-flanking sequence. Additionally, a CCTCCC sequence, which increases the transcriptional activity of the SM1/2 gene in smooth muscle, is located 27 bp upstream of the TATA-like sequence, a location identical to that found in the SM1/2 5'-flanking region. However, the promoter directed equivalent expression when transfected into smooth muscle and other cell types. Analysis of the hSlo beta subunit 5'-flanking region revealed a TATA box at position -77 and maximum promoter activity (up to 11.0-fold) in a 200 bp region upstream from the cap site. Binding sites for GATA-1, Myo-D, c-myb, Ets-1/Elk-1, Ap-1, and Ik-2 were identified within this sequence. Two CCTCCC elements are present in the hSlo beta subunit promoter, but tissue-specific transcriptional activity was not observed. The lack of tissue-specific promoter activity, particularly the finding of promoter activity in cells from tissues in which the maxiK gene is not expressed, suggests a complex channel regulatory mechanism for hSlo genes. Moreover, the lack of similarity of the promoters of the two genes suggests that regulation of coordinate expression of the subunits does not occur through equivalent cis-acting sequences.  (+info)

Genomic organization of the KCNQ1 K+ channel gene and identification of C-terminal mutations in the long-QT syndrome. (5/9961)

The voltage-gated K+ channel KVLQT1 is essential for the repolarization phase of the cardiac action potential and for K+ homeostasis in the inner ear. Mutations in the human KCNQ1 gene encoding the alpha subunit of the KVLQT1 channel cause the long-QT syndrome (LQTS). The autosomal dominant form of this cardiac disease, the Romano-Ward syndrome, is characterized by a prolongation of the QT interval, ventricular arrhythmias, and sudden death. The autosomal recessive form, the Jervell and Lange-Nielsen syndrome, also includes bilateral deafness. In the present study, we report the entire genomic structure of KCNQ1, which consists of 19 exons spanning 400 kb on chromosome 11p15.5. We describe the sequences of exon-intron boundaries and oligonucleotide primers that allow polymerase chain reaction (PCR) amplification of exons from genomic DNA. Two new (CA)n repeat microsatellites were found in introns 10 and 14. The present study provides helpful tools for the linkage analysis and mutation screening of the complete KCNQ1 gene. By use of these tools, five novel mutations were identified in LQTS patients by PCR-single-strand conformational polymorphism (SSCP) analysis in the C-terminal part of KCNQ1: two missense mutations, a 20-bp and 1-bp deletions, and a 1-bp insertion. Such mutations in the C-terminal domain of the gene may be more frequent than previously expected, because this region has not been analyzed so far. This could explain the low percentage of mutations found in large LQTS cohorts.  (+info)

Angiotensin II type 1 receptor-mediated inhibition of K+ channel subunit kv2.2 in brain stem and hypothalamic neurons. (6/9961)

Angiotensin II (Ang II) has powerful modulatory actions on cardiovascular function that are mediated by specific receptors located on neurons within the hypothalamus and brain stem. Incubation of neuronal cocultures of rat hypothalamus and brain stem with Ang II elicits an Ang II type 1 (AT1) receptor-mediated inhibition of total outward K+ current that contributes to an increase in neuronal firing rate. However, the exact K+ conductance(s) that is inhibited by Ang II are not established. Pharmacological manipulation of total neuronal outward K+ current revealed a component of K+ current sensitive to quinine, tetraethylammonium, and 4-aminopyridine, with IC50 values of 21.7 micromol/L, 1.49 mmol/L, and 890 micromol/L, respectively, and insensitive to alpha-dendrotoxin (100 to 500 nmol/L), charybdotoxin (100 to 500 nmol/L), and mast cell degranulating peptide (1 micromol/L). Collectively, these data suggest the presence of Kv2.2 and Kv3.1b. Biophysical examination of the quinine-sensitive neuronal K+ current demonstrated a macroscopic conductance with similar biophysical properties to those of Kv2.2 and Kv3.1b. Ang II (100 nmol/L), in the presence of the AT2 receptor blocker PD123,319, elicited an inhibition of neuronal K+ current that was abolished by quinine (50 micromol/L). Reverse transcriptase-polymerase chain reaction analysis confirmed the presence of Kv2.2 and Kv3.1b mRNA in these neurons. However, Western blot analyses demonstrated that only Kv2.2 protein was present. Coexpression of Kv2.2 and the AT1 receptor in Xenopus oocytes demonstrated an Ang II-induced inhibition of Kv2.2 current. Therefore, these data suggest that inhibition of Kv2.2 contributes to the AT1 receptor-mediated reduction of neuronal K+ current and subsequently to the modulation of cardiovascular function.  (+info)

Ionic currents underlying spontaneous action potentials in isolated cerebellar Purkinje neurons. (7/9961)

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)

Inducible genetic suppression of neuronal excitability. (8/9961)

Graded, reversible suppression of neuronal excitability represents a logical goal of therapy for epilepsy and intractable pain. To achieve such suppression, we have developed the means to transfer "electrical silencing" genes into neurons with sensitive control of transgene expression. An ecdysone-inducible promoter drives the expression of inwardly rectifying potassium channels in polycistronic adenoviral vectors. Infection of superior cervical ganglion neurons did not affect normal electrical activity but suppressed excitability after the induction of gene expression. These experiments demonstrate the feasibility of controlled ion channel expression after somatic gene transfer into neurons and serve as the prototype for a novel generalizable approach to modulate excitability.  (+info)

TY - JOUR. T1 - ATP sensitive potassium channel openers. T2 - A new class of ocular hypotensive agents. AU - Roy Chowdhury, Uttio. AU - Dosa, Peter I.. AU - Fautsch, Michael P. PY - 2016/3/2. Y1 - 2016/3/2. N2 - ATP sensitive potassium (KATP) channels connect the metabolic and energetic state of cells due to their sensitivity to ATP and ADP concentrations. KATP channels have been identified in multiple tissues and organs of the body including heart, pancreas, vascular smooth muscles and skeletal muscles. These channels are obligatory hetero-octamers and contain four sulfonylurea (SUR) and four potassium inward rectifier (Kir) subunits. Based on the particular type of SUR and Kir present, there are several tissue specific subtypes of KATP channels, each with their own unique set of functions. Recently, KATP channels have been reported in human and mouse ocular tissues. In ex vivo and in vivo model systems, KATP channel openers showed significant ocular hypotensive properties with no appearance of ...
Shop Probable potassium channel protein ELISA Kit, Recombinant Protein and Probable potassium channel protein Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
TY - JOUR. T1 - Blockade of ATP-sensitive potassium channels prevents the attenuation of the exercise pressor reflex by tempol in rats with ligated femoral arteries. AU - Yamauchi, Katsuya. AU - Stone, Audrey J.. AU - Stocker, Sean D.. AU - Kaufman, Marc P.. PY - 2012/8/1. Y1 - 2012/8/1. N2 - We reported previously that tempol attenuated the exercise pressor and muscle mechanoreceptor reflexes in rats whose femoral arteries were ligated, whereas tempol did not attenuate these reflexes in rats whose femoral arteries were freely perfused. Although the mechanism whereby tempol attenuated these reflexes in rats whose femoral artery was ligated was independent of its ability to scavenge reactive oxygen species, its nature remains unclear. An alternative explanation for the tempol-induced attenuation of these reflexes involves ATP-sensitive potassium channels (K Atp) and calcium-activated potassium channels (BK Ca), both of which are opened by tempol. We tested the likelihood of this explanation by ...
Carr DB, McDonnell Moorehead T, Bouchard A, et al. Effects of injectable HPβCD-diclofenac on the human delayed rectifier potassium channel current in vitro and on proarrhythmic QTc in vivo. Clin Ther. 2013;35(5):646-658. doi:10.1016/j.clinthera.2013.03.014. View article
Most information currently available regarding vascular K+ channel function in diabetes concerns KATP channels. As for chronic hypertension, there are now several reports of impaired vascular relaxant responses to synthetic openers of KATP channels in long-term diabetes. These studies have mostly utilized the streptozotocin-injected rat model of diabetes and have examined vessels at 2.5 to 4 months after streptozotocin treatment. In this model in which plasma glucose levels are increased 3- to 4-fold, impaired relaxation of the isolated aorta122 123 124 and mesenteric vascular bed125 and reduced dilatation of large126 and small127 cerebral arteries in vivo typically develop. These changes are thought to be the result of a decreased number of vascular KATP channels and/or reduced sensitivity of these channels to synthetic openers. Nonspecific cytotoxic effects of streptozotocin seem an unlikely cause of these changes because, like other manifestations of vascular dysfunction, abnormal vasodilator ...
Most information currently available regarding vascular K+ channel function in diabetes concerns KATP channels. As for chronic hypertension, there are now several reports of impaired vascular relaxant responses to synthetic openers of KATP channels in long-term diabetes. These studies have mostly utilized the streptozotocin-injected rat model of diabetes and have examined vessels at 2.5 to 4 months after streptozotocin treatment. In this model in which plasma glucose levels are increased 3- to 4-fold, impaired relaxation of the isolated aorta122 123 124 and mesenteric vascular bed125 and reduced dilatation of large126 and small127 cerebral arteries in vivo typically develop. These changes are thought to be the result of a decreased number of vascular KATP channels and/or reduced sensitivity of these channels to synthetic openers. Nonspecific cytotoxic effects of streptozotocin seem an unlikely cause of these changes because, like other manifestations of vascular dysfunction, abnormal vasodilator ...
Potassium channel molecule. Computer model showing the structure of a bacterial potassium channel with four units arranged around an axis going through the first (and only visible) of four potassium ions (big purple sphere). From Bacillus cereus. - Stock Image C035/8257
A recent study (1) gives insight into how the lipids in the cell membranes affect how well one particular potassium channel functions. The particular channel the researchers investigated is one of the most studied potassium channels. This channel demonstrates how the function of other channels and pumps also may be affected by the composition of the cell membranes.. The researchers showed that the pore that lets potassium flow through the channel is fine-tuned by the physical characteristics of the lipid in the cell membrane. When the membrane allows protein in the pore of the channel to change more easily, potassium can get through faster.. This study changed two characteristics of the membrane that potassium channels sit in. The two characteristics of the membrane that the researchers changed were the temperature of the membrane, and the type of fats the membrane was made of. Both of these characteristics changed the fluidity of the membrane.. The researchers then determined whether the ...
An electrochemical gating model is presented to account for the effects described in the companion paper by M. R. Silver, M. S. Shapiro, and T. E. DeCoursey (1994. Journal of General Physiology, 103:519-548) of Rb+ and Rb+/K+ mixtures on the kinetics and voltage dependence of an inwardly rectifying (IR) K+ channel. The model proposes that both Rb+ and K+ act as allosteric modulators of an intrinsically voltage dependent isomerization between open and closed states. Occupancy of binding sites on the outside of the channel promotes channel opening and stabilizes the open state. Rb+ binds to separate sites within the pore and plugs IR channels. Occupancy of the pore by Rb+ can modify the rates of isomerization and the affinity of the allosteric sites for activator ions. The model also incorporates the proposed triple-barreled nature of the IR channel (Matsuda, H., 1988. Journal of Physiology. 397:237-258.) by proposing that plugging of the channel is a cooperative process involving a single site in ...
Global Markets Directs, Potassium Voltage Gated Channel Subfamily C Member 1 (Voltage Gated Potassium Channel Subunit Kv3.1 or Voltage Gated Potassium Channel Subunit Kv4 or KCNC1) - Pipeline
This enabled them to draw conclusions about its mechanism of action, which they describe in the current issue of "Nature Communications". Neurons conduct information by way of electrical impulses through our body. Potassium channels are a key component of this electrical circuit and are controlled either by an electrical impulse or through signaling molecules. In man, the dysfunction of the so-called HCN potassium channels is associated with neurological disorders such as epilepsy and depression. Prof. Henning Stahlbergs team at the Biozentrum of the University of Basel has now elucidated the full structure of a bacterial counterpart of this type of potassium channel, which has provided new insights into its functioning.. ...
This e-book presents an overview of the different substances capable of modulating potassium channels in relation to various clinical indications in cardiology, pulmonology, endocrinology and neurology. The possible benefits and side effects of potassium channel modulators is discussed in correlation with biophysical and pharmacological properties of ion channels. Readers will learn how mutation of K+ channels can be conferred by molecular processes such as alternative splicing, RNA editing and posttranslational modifications. Altogether, this e-book will be of use to clinical practitioners, electrophysiologists and pharmacologists interested in the complicated but fascinating science of potassium channels.. ...
Energy dissipating systems (uncoupling proteins - UCPs, alternative oxidase - AOX, mitochondrial potassium channels) in physiological and pathological conditions: the activity of UCPs and AOXs in different eukaryotic organisms, UCP proteins in inflammation and circulatory diseases, mitochondrial potassium channels in cytoprotection, mitochondria and the endurance ...
July 29, 2013. Just 12 molecules of water cause the long post-activation recovery period required by potassium ion channels before they can function again. Using molecular simulations that modeled a potassium channel and its immediate cellular environment, atom for atom, University of Chicago scientists have revealed this new mechanism in the function of a nearly universal biological structure, with implications ranging from fundamental biology to the design of pharmaceuticals. Their findings were published online July 28 in Nature.. "Our research clarifies the nature of this previously mysterious inactivation state. This gives us better understanding of fundamental biology and should improve the rational design of drugs, which often target the inactivated state of channels" said Benoît Roux, PhD, professor of biochemistry and molecular biology at the University of Chicago.. Potassium channels, present in the cells of virtually all living organisms, are core components in bioelectricity ...
Effects of KRN4884 (5-amino-,i,N,/i,-[2-(2-chlorophenyl)ethyl]-,i,N,/i,-cyano-3-pyridinecarboxamidine), a novel K,sup,+,/sup, channel opener, on ionic currents were examined in rabbit femoral arterial myocytes (RFAMs). Under whole-cell clamp conditions where cells were superfused with 5.9 mM K,sup,+,/sup, bathing solution, KRN4884 elicited an outward current at −30 mV. KRN4884-induced current had a reversal potential of −78 mV and was abolished by application of glibenclamide (glib). KRN4884 was approximately 43 times more potent than levcromakalim in activating an ATP-sensitive K,sup,+,/sup, current (I,sub,K-ATP,/sub,). On the other hand, KRN4884 affected neither voltage-dependent Ca,sup,2+,/sup, nor delayed rectifier K,sup,+,/sup, channel currents. In the inside-out patch clamp configuration where cells were superfused with the symmetrical 140 mM K,sup,+,/sup, solution, KRN4884 activated 47 pS K,sup,+,/sup, channels in the presence of adenosine diphosphate. Similar 47 pS K,sup,+,/sup, ...
The following figure shows the location of the disease-causing mutations in hKv8.2 in CDSRE patients examined in this study. Three of these, W450G, G459D, and G461R, are located in the pore region of the hKv8.2 α-subunit. The missense mutations G459D and G461R affect the first and second glycine, respectively, of the Gly-Tyr-Gly motif, the characteristic potassium channel signature sequence. To understand the functional consequences of these mutations, the corresponding mutations (W467G, G476D, and G478R) were introduced into mKv8.2, and their effect on subunit localization in COS7L cells was examined. Like mKv8.2, the expression of either mKv8.2-W467G-EGFP, mKv8.2-G476D-EGFP, or mKv8.2-G478R-EGFP resulted in an intracellular localization [1753]. Voltage-gated K+ channels selectively transfer potassium ions through the plasma membrane in response to depolarization. The ion-conducting core of voltage-gated K+ channels is composed of four Kv-alpha subunits, which also possess the voltage sensor. ...
Potassium channels selectively conduct K(+) ions across cell membranes and have key roles in cell excitability. Their opening and closing can be spontaneous or controlled by membrane voltage or ligand binding. We used Ba(2+) as a probe to determine the location of the ligand-sensitive gate in an inwardly rectifying K(+) channel (Kir6.2). To a K(+) channel, Ba(2+) and K(+) are of similar sizes, but Ba(2+) blocks the pore by binding within the selectivity filter. We found that internal Ba(2+) could still access its binding site when the channel was shut, which indicates that the ligand-sensitive gate lies above the Ba(2+)-block site, and thus within or above the selectivity filter. This is in marked contrast to the voltage-dependent gate of K(V) channels, which is located at the intracellular mouth of the pore.
Gene Information Potassium channels are present in most mammalian cells where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein which has a greater tendency to allow potassium to flow into a cell rather than out of a cell is controlled by G-proteins. It associates with another G-protein-activated potassium channel to form a heteromultimeric pore-forming complex. [provided by RefSeq Jul 2008]. ...
This review has focused on the properties of the ATP-sensitive K-channel found in cardiac and skeletal muscle, and in pancreatic beta-cells. It is conceivable that this channel will be found in other cell types. In particular, it would be worthwhile looking for its presence in those cells in which electrical activity is linked to metabolism, glucose concentration, or oxygen levels. Obvious examples are the glucoreceptor neurons of mammalian brain and chemoreceptors such as those of the carotid body. While ATP-sensitive K-channels in cardiac and skeletal muscle membranes are rather similar, there are a few significant differences between these channels and that found in the beta-cell. Most notably, the latter is more sensitive to inhibition by ATP and sulphonylureas. It remains to be seen whether they also differ in the ability of nucleotides to activate the channel. Considerable confusion also still surrounds the physiological regulation of the ATP-sensitive K-channel in intact cells. Although the
This gene encodes one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. The message for this gene is mainly expressed in the cortical distal tubules and collecting ducts of the kidney. The protein is highly sensitive to external pH and this, in combination with its expression pattern, suggests it may play an important role in renal potassium transport ...
Potassium channel (Protein Data Bank entry 1bl8) on a dark slate blue background with potassium ions shown in firebrick. The channel is comprised of four chains. Each chain has been rainbow-colored from blue at the N-terminus to red at the C-terminus, but only the surface of the channel is shown. The surface has been sliced with a per-model clipping plane. The surface cap color is plum except with opacity set to 0.8. The shininess and brightness have been set to 128 and 8, respectively, and the lights on the scene have been moved from their default positions. The subdivision quality (related to the smoothness of the spherical ions) is 5.0, and the molecular surface was computed with probe radius and vertex density set to 1.0 and 6.0, respectively. The entry Cavity and Tunnel Detection provides additional views of the same structure. ...
This is the Authors Original Manuscript of an article published by Taylor & Francis in Channels on 02 Jan 2018 available online: https://doi.org/10.1080/19336950.2017.1412151 ...
... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
BioAssay record AID 2432 submitted by Johns Hopkins Ion Channel Center: Mode of action assay - molecular determinants for ztz240, a potentiator of KCNQ2 potassium channels.
BioAssay record AID 2258 submitted by Johns Hopkins Ion Channel Center: Summary of probe development for potentiators of KCNQ2 potassium channels.
Kv1.2 Potassium Channel information including symptoms, causes, diseases, symptoms, treatments, and other medical and health issues.
High quality reagents for receptor, ion channel and enzyme research including potassium channel tools from Hello Bio - a trusted, affordable life science reagents supplier.
Differences in the mechanism of metabolic regulation of ATP-sensitive K+ channels containing Kir6.1 and Kir6.2 subunits.: Kir6.1\SUR2B has intrinsic sensitivity
心不全によるK_,ATP,チャネルの変調 : レシピエントから得た心筋による検討 Alterations in ATP-sensitive potassium channel sensitivity to ATP in failing human hearts ...
Experiments described in this report provide a strong argument for the existence of two distinct current components (I KF andI KS) in the slow sustained voltage-activated K+ current (I K) in the larval muscles ofDrosophila. Voltage-activated K+ current in the larval muscles ofDrosophila has been previously resolved into two distinct currents. With the data presented here, we can now resolve the total voltage-activated K+ current into three components. Resolution of I K intoI KS andI KF will be particularly helpful in analyzing the properties of these two currents, deciphering the functional role of each current in muscle excitability, and studying mechanisms underlying their function and regulation.. Channels carrying I KS are encoded by the Shab gene. I KS shares properties with the current generated by expressing Shabchannels in Xenopus oocytes. These properties include relative resistance to blockade by 4-AP and a relatively slow activation (Covarrubias et al., 1991; Tsunoda and Salkoff, ...
Our laboratory studies potassium channels which are key elements which control and shape electrical activity in the brain, heart, and other excitable tissues. These channels are major determinants of behavior and higher brain function. The potassium channels we study are involved in human disease (e.g. epilepsy, cardiac arrhythmia), basic physiology (e.g. control of blood pressure, protection from hypoxia), and higher brain function (e.g. learning and memory). Our approach is a comparative genom
The protein encoded by this gene is part of a potentially heterotetrameric voltage-independent potassium channel that is activated by intracellular calcium. Activation is
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Tumor necrosis factor alpha modulates sodium-activated potassium channel SLICK in rat dorsal horn neurons via p38 MAPK activation pathway Kun Wang,1 Feng Wang,1 Jun-Ping Bao,2 Zhi-Yang Xie,1 Lu Chen,1 Bao-Yi Zhou,1 Xin-Hui Xie,2 Xiao-Tao Wu1,2 1Medical School of Southeast University, 2Department of Orthopaedics, Zhongda Hospital, Southeast University, Nanjing, Peopleâ s Republic of China Abstract: The dorsal horn (DH) of the spinal cord is the integrative center that processes and transmits pain sensation. Abnormal changes in ion channel expression can enhance the excitability of pain-related DH neurons. Sodium-activated potassium (KNa) channels are highly expressed particularly in the central nervous system; however, information about whether rat DH neurons express the SLICK channel protein is lacking, and the direct effects on SLICK in response to inflammation and the potential signaling pathway mediating such effects are yet to be elucidated. Here, using cultured DH neurons, we have shown that
This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by external barium (By similarity).
This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium. Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation (By similarity).
Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. KCNJ16 may be involved in the regulation of fluid and pH balance. In the kidney, together with KCNJ10, mediates basolateral K(+) recycling in distal tubules; this process is critical for Na(+) reabsorption at the tubules (PubMed:24561201 ...
Potassium channels, found throughout the animal and plant kingdoms, play important roles in maintaining membrane potentials and regulating action potential firing, shape, and duration, among other functions. Using the Xenopus laevis (frog) oocyte as model system, we induced high expression of sodium and potassium voltage-gated channels and recorded action potentials by a modification of the two-electrode voltage-clamp recording technique. The voltage-dependent sodium conductance was due to expression of the skeletal muscle NaV channel (NaV1.4) and the delayed rectifier voltage-dependent potassium conductance was due to expression of a Shaker (Kv1) potassium channel. Upon this background, we mixed different potassium-selective ion channels, such as inwardly rectifying potassium (KIR) channels, tandem pore domain (K2P) potassium channels and voltage-gated (KV) channels. We analyzed how these potassium channels affected firing thresholds, reliability of action potential generation, action potential
OBJECTIVE: To assess the influence of blocking smooth muscle large conductance Ca(2+) -activated K+ channels and voltage-gated K+ channels on the conducted dilation to ACh and isoproterenol. MATERIALS AND METHODS: Rat mesenteric arteries were isolated with a bifurcation, triple-cannulated, pressurized and imaged using confocal microscopy. Phenylephrine was added to the superfusate to generate tone, and agonists perfused into a sidebranch to evoke local dilation and subsequent conducted dilation into the feed artery. RESULTS: Both ACh- and isoproterenol-stimulated local and conducted dilation with similar magnitudes of decay with distance along the feed artery (2000μm: ∼15% maximum dilation). The gap junction uncoupler carbenoxolone prevented both conducted dilation and intercellular spread of dye through gap junctions. IbTx, TEA or 4-AP, blockers of large conductance Ca(2+) -activated K+ channels and voltage-gated K+ channels, did not affect conducted dilation to either agonist. A combination
TY - JOUR. T1 - Spontaneous contractions of the pig urinary bladder. T2 - The effect of ATP-sensitive potassium channels and the role of the mucosa. AU - Akino, Hironobu. AU - Chapple, Christopher R.. AU - McKay, Neil G.. AU - Cross, Rebecca L.. AU - Murakami, Shigetaka. AU - Yokoyama, Osamu. AU - Chess-Williams, Russell. AU - Sellers, Donna J.. PY - 2008/11. Y1 - 2008/11. N2 - OBJECTIVE: To investigate the influence of the mucosa on the inhibitory effects of the ATP-sensitive potassium channel (KATP channel) opener, cromakalim, on the spontaneous contractions of pig bladder strips from the bladder dome and trigone. Little is known about the influence of the mucosa on spontaneous contractions and whether the nature of these contractions differs between the bladder dome and trigone. MATERIALS AND METHODS: Paired longitudinal strips of female pig bladders were isolated from the dome and trigone. The mucosa was removed from one strip per pair and tissues were set up in organ baths. Spontaneous ...
The ATP-dependent potassium channels (KATP channels) were originally identified in isolated membrane patches prepared from guinea pig ventricular myocytes by Noma1 in 1983. Since their discovery in cardiac cells, KATP channels have also been discovered in many other tissues, such as smooth muscle, skeletal muscle, pancreas, and brain, in which they have been shown to couple cellular metabolism to membrane electrical activity.2 Primarily on the basis of studies using pharmacological tools, openers of KATP channels have been shown to elicit cardioprotective effects, whereas KATP channel antagonists have been shown to block the cardioprotective effects of KATP channel openers and the powerful protective effect produced by single or multiple brief episodes of ischemia to reduce myocardial infarct size, a phenomenon called ischemic preconditioning.3 Because the results of these previous studies were obtained indirectly by the use of pharmacological agonists and antagonists, the results of the present ...
TY - JOUR. T1 - Voltage-dependent potassium currents during fast spikes of rat cerebellar Purkinje neurons. T2 - Inhibition by BDS-I toxin. AU - Martina, Marco. AU - Metz, Alexia E.. AU - Bean, Bruce P.. PY - 2007/1/1. Y1 - 2007/1/1. N2 - We characterized the kinetics and pharmacological properties of voltage-activated potassium currents in rat cerebellar Purkinje neurons using recordings from nucleated patches, which allowed high resolution of activation and deactivation kinetics. Activation was exceptionally rapid, with 10-90% activation in about 400 μs at +30 mV, near the peak of the spike. Deactivation was also extremely rapid, with a decay time constant of about 300 μs near -80 mV. These rapid activation and deactivation kinetics are consistent with mediation by Kv3-family channels but are even faster than reported for Kv3-family channels in other neurons. The peptide toxin BDS-I had very little blocking effect on potassium currents elicited by 100-ms depolarizing steps, but the potassium ...
Potassium voltage-gated channel subfamily D member 2 is a protein that in humans is encoded by the KCND2 gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential. Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the ...
Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Eight transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2013 ...
In a previous study we reported the presence of a large conductance K+ channel in the membrane of endoplasmic reticulum (ER) from rat hepatocytes. The channel open probability (Po) appeared voltage dependent and reached to a minimum 0.2 at +50 mV. Channel activity in this case was found to be totally inhibited at ATP concentration 2.5 mM, glibenclamide 100 μM and tolbutamide 400 μM. Existing evidence indicates an impairment of endoplasmic reticulum functions in ER stress condition. Because ER potassium channels have been involved in several ER functions including cytoprotection, apoptosis and calcium homeostasis, a study was carried out to consider whether the ER potassium channel function is altered in a high fat diet model of ER stress. Male Wistar rats were made ER stress for 2 weeks with a high fat diet. Ion channel incorporation of ER stress model into the bilayer lipid membrane allowed the characterization of K+ channel. Our results indicate that the channel Po was significantly ...
TY - JOUR. T1 - Up-regulation of A-type potassium currents protects neurons against cerebral ischemia. AU - Deng, Ping. AU - Pang, Zhi Ping. AU - Lei, Zhigang. AU - Shikano, Sojin. AU - Xiong, Qiaojie. AU - Harvey, Brandon K.. AU - London, Barry. AU - Wang, Yun. AU - Li, Min. AU - Xu, Zao C.. PY - 2011/9/1. Y1 - 2011/9/1. N2 - Excitotoxicity is the major cause of many neurologic disorders including stroke. Potassium currents modulate neuronal excitability and therefore influence the pathological process. A-type potassium current (IA) is one of the major voltage-dependent potassium currents, yet its roles in excitotoxic cell death are not well understood. We report that, following ischemic insults, the IA increases significantly in large aspiny (LA) neurons but not medium spiny (MS) neurons in the striatum, which correlates with the higher resistance of LA neurons to ischemia. Activation of protein kinase Cα increases IA in LA neurons after ischemia. Cultured neurons from transgenic mice lacking ...
Cerebellar granule neurons (CGNs) are one of the most populous cells in the mammalian brain. They express an outwardly rectifying potassium current, termed a
Read "Kinetic Analysis of the Inhibitory Effect of Glibenclamide on KATP Channels of Mammalian Skeletal Muscle, The Journal of Membrane Biology" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
The anti-contractile effect of perivascular adipose tissue (PVAT) is an important mechanism in the modulation of vascular tone in peripheral arteries. Recent evidence has implicated the XE991-sensitive voltage-gated Kv (KCNQ) channels in the regulation of arterial tone by PVAT. However, until now the in vivo pharmacology of the involved vascular Kv channels with regard to XE991 remains undetermined, since XE991 effects may involve Ca2+ activated BKCa channels and/or voltage-dependent Kv1.5 channels sensitive to diphenyl phosphine oxide-1 (DPO-1). In this study, we tested whether Kv1.5 channels are involved in the control of mesenteric arterial tone and its regulation by PVAT. Our study was also aimed at extending our current knowledge on the in situ vascular pharmacology of DPO-1 and XE991 regarding Kv1.5 and BKCa channels, in helping to identify the nature of K+ channels that could contribute to PVAT-mediated relaxation. XE991 at 30 µM reduced the anti-contractile response of PVAT, but had no effects
Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. It plays an essential role in T-cell proliferation and activation. This gene appears to be intronless and it is clustered together with KCNA2 and KCNA10 genes on chromosome 1.
Two-pore potassium channels (K2Ps) activation[edit]. *Two-pore potassium channels (K2Ps) modulate the potassium conductance ... This drug-elicited channel activation has been shown to be dependent upon specific amino-acids within certain K2P channels (i.e ... The K2P channel family comprises six subfamilies, which includes 15 unique members. 13 of these channels (excluding TWIK-1 and ... Opening of these channels therefore facilitates a hyperpolarizing current, which reduces neuronal excitability. K2Ps have been ...
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 ...
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 ... One gap junction channel is composed of two connexons (or hemichannels), which connect across the intercellular space.[4][5][6] ...
When a Gβγ or Gα(GTP) molecule binds to the C-terminus of the potassium channel, it becomes active, and potassium ions are ... The activation of the potassium channel and subsequent deactivation of the calcium channel causes membrane hyperpolarization. ... Yamada M, Inanobe A, Kurachi Y (December 1998). "G protein regulation of potassium ion channels". Pharmacological Reviews. 50 ( ... Embedded in the cell membrane is also the G protein-coupled inwardly-rectifying potassium channel. ...
Potassium channel (Kv7) opener.[116]. PO, rectal.. Bioavailability = 90% (oral), 72.5% (rectal); protein binding = 80%; volume ... Comes in potassium and free acid forms; degrades upon contact with light. Propionic acid derivative.. As per diclofenac.. PO.. ... N-type calcium-channel blocker.. Intrathecal.. Protein binding = 50%; half-life = 2.9-6.5 hours; excretion = urine (,1%).[122] ... Flupirtine is a centrally acting K+ channel opener with weak NMDA antagonist properties.[34] It is used in Europe for moderate ...
Doxapram blocks leak potassium channels in the Tandom pore domain family of potassium channels while GAL-021 blocks BK channels ... Two common potassium channel blockers are Doxapram and GAL-021. Both act on potassium channels in Carotid Bodies. These cells ... Blocking the potassium channels on the membranes of these cells effectively depolarizes the membrane potential, which in turn ... Analeptics can act as potassium channel blockers, ampakines, and serotonin receptor agonists, and adenosine antagonism. ...
August 2005). "The voltage-gated potassium channel Kv1.3 is highly expressed on inflammatory infiltrates in multiple sclerosis ... Beeton C, Chandy KG (December 2005). "Potassium channels, memory T cells, and multiple sclerosis". Neuroscientist. 11 (6): 550- ... June 2003). "The voltage-gated Kv1.3 K(+) channel in effector memory T cells as new target for MS". J. Clin. Invest. 111 (11): ...
Potassium channels demonstrate a seemingly counterintuitive activity: they permit the passage of potassium ions, whereas they ... These channels are of particular importance to the nervous system and the heart and enable potassium ions to cross the cell ... In 1989 he was appointed assistant professor at Harvard University where he studied the interaction of the potassium channel ... Before MacKinnon's work, the detailed molecular architecture of potassium channels and the exact means by which they conduct ...
... s express potassium channels at a high density. When neurons are active, they release potassium, increasing the local ... Walz W (2000). "Role of astrocytes in the clearance of excess extracellular potassium". Neurochemistry International. 36 (4-5 ... Because astrocytes are highly permeable to potassium, they rapidly clear the excess accumulation in the extracellular space.[17 ... Abnormal accumulation of extracellular potassium is well known to result in epileptic neuronal activity.[18] ...
MiRP2 - β subunit to voltage-gated potassium channels. Modulates the transient outward potassium current Ito. [17] ... while others form different types of sodium channel (SCN10A). Some genes encode ion channels that carry calcium or potassium ... KVβ2, voltage-gated potassium channel β2 subunit - mutation increases Ito. [17] ... KV4.3, α-subunit of the transient outward potassium channel Ito.[6] ...
... 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 ... "Entrez Gene: KCNA1 potassium voltage-gated channel".. *^ "KCNA1 - Potassium voltage-gated channel subfamily A member 1 - Homo ...
By blocking specifically the Kv4 channels, AmmTX3 reduces the A-type potassium current through these channels almost completely ... A-type potassium currents can be generated by Kv1.4, Kv3.3, Kv3.4, all members of Kv4 and Erg3 channels. The influence of ... The toxin is known for its ability to act as a specific Kv4 channel blocker, and thereby reducing the A-type potassium current ... Bougis, PE; Martin-Eauclaire, MF (25 June 2015). "Shal-type (Kv4.x) potassium channel pore blockers from scorpion venoms". ...
These ATP-sensitive potassium ion channels are normally open and the calcium ion channels are normally closed.[3] Potassium ... Voltage-gated calcium channels and ATP-sensitive potassium ion channels are embedded in the plasma membrane of beta cells.[7][8 ... The ATP-sensitive potassium ion channels close when this ratio rises.[8] This means that potassium ions can no longer diffuse ... Sulfonylureas are insulin secretagogues that act by closing the ATP-sensitive potassium channels, thereby causing insulin ...
... is a potassium channel-opening vasodilator. The active isomer is levcromakalim. It acts on ATP-sensitive potassium channels and ...
Carta, Mario (2014). "Membrane Lipids Tune Synaptic Transmission by Direct Modulation of Presynaptic Potassium Channels". ...
Fluoroquinolones prolong the heart's QT interval by blocking voltage-gated potassium channels.[33] Prolongation of the QT ...
KCNJ2: potassium inwardly-rectifying channel, subfamily J, member 2 (17q24.3). *ACTG1: actin, gamma 1 (17q25) ... TRPV1: encoding protein Transient receptor potential cation channel subfamily V member 1 ... TMC6 and TMC8: Transmembrane channel-like 6 and 8 (epidermodysplasia verruciformis) (17q25.3) ...
Examples include coupling to and activating G protein-coupled inwardly-rectifying potassium channels. ... ion channels, transporter proteins, and other parts of the cell machinery, controlling transcription, motility, contractility, ...
Antibiodies against the Kir4.1 potassium channel may be related to MS.[144] ...
... in potassium channel antibodies and myelin basic antibodies, and 91% in calcium channel antibodies. This model allowed the ... It was found that the potassium channels were being blocked so that inflammation was occurring at the nerve root and causing ... Researchers determined that the irritation was due to the voltage-gated potassium channels being blocked. They identified 125 1 ... "Potassium channel complex autoimmunity induced by inhaled brain tissue aerosol". Annals of Neurology. 71 (3): 417-426. doi: ...
Bergapten has also been implicated as a potassium channel blocker; in one case study, a patient who consumed four litres of ...
calcium channel activity. • metal ion binding. • voltage-gated ion channel activity. • ion channel activity. • protein binding ... voltage-gated calcium channel activity involved in cardiac muscle cell action potential. • high voltage-gated calcium channel ... When calcium ions bind to calmodulin, which in turn binds to a Cav1.2 channel, it allows the Cav1.2 channels within a cluster ... This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ...
ion channel activity. • protein binding. • actin binding. • calcium channel activity. • cation channel activity. • protein ... Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene encoding a protein of ... 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. • ...
voltage-gated ion channel activity. • channel regulator activity. • calcium channel activity. • voltage-gated calcium channel ... Voltage-dependent calcium channel gamma-4 subunit is a protein that in humans is encoded by the CACNG4 gene.[5][6] ... voltage-gated calcium channel complex. • integral component of membrane. • integral component of plasma membrane. • AMPA ... calcium channel regulator activity. • ionotropic glutamate receptor binding. Cellular component. • endocytic vesicle membrane. ...
ion channel activity. • store-operated calcium channel activity. • protein binding. • calcium channel activity. • clathrin ... calcium channel complex. • membrane. • cytoplasm. • growth cone. • neuronal cell body. • dendrite. • membrane raft. • cation ... Short transient receptor potential channel 5 (TrpC5) also known as transient receptor protein 5 (TRP-5) is a protein that in ... "Entrez Gene: transient receptor potential cation channel".. *^ Sossey-Alaoui K, Lyon JA, Jones L, Abidi FE, Hartung AJ, Hane B ...
Voltage sensitive ion channels are glycoprotein molecules which extend through the lipid bilayer, allowing ions to traverse ... under certain conditions through the axolemma), the fast-acting sodium and the inward-rectifying potassium. Though successful ...
Term: small/intermediate conductance calcium-activated potassium channel protein. ID: PIRSF038511 Mouse Protein Superfamily ...
... by inwardly rectifying potassium channel, voltage-gated potassium channel (Kv), or BK currents. The KCa3.1 whole-cell ... Yamashita M., Sugioka M., Ogawa Y. (2006) Voltage- and Ca2+-activated potassium channels in Ca2+ store control Ca2+ release. ... calcium-activated potassium channel. CREB. cAMP-response element-binding protein. CsA. cyclosporin A. EBIO. 1-ethyl-2- ... Neylon C. B. (2002) Potassium channels and vascular proliferation. Vascul. Pharmacol. 38, 35-41 [PubMed] ...
... channel; TREK2, TWIK-related K+ channel type 2; TRESK, TWIK-related spinal cord K+ channel. ... We hypothesize that HFD causes an upregulation of 2-pore domain potassium channels, resulting in hyperpolarization of nodose ... High-fat diet-induced vagal afferent dysfunction via upregulation of 2-pore domain potassium TRESK channel. ... High-fat diet-induced vagal afferent dysfunction via upregulation of 2-pore domain potassium TRESK channel. ...
They express an outwardly rectifying potassium current, termed a ... A Functional Role for the Two-Pore Domain Potassium Channel ... This description of a functional two-pore domain potassium channel in the mammalian central nervous system indicates its ... A Functional Role for the Two-Pore Domain Potassium Channel TASK-1 in Cerebellar Granule Neurons. Proceedings of the National ... but it is insensitive to the classical broad-spectrum potassium channel blocking drugs 4-aminopyridine and tetraethylammonium ...
The drug will then open the potassium channels which enables cell membrane hyperpolarization and the expansion of the blood ...
Inward rectifier potassium channels.. Nichols CG1, Lopatin AN.. Author information. 1. Department of Cell Biology and ... ATP-sensitive K channels, and muscarinic receptor-activated K channels. High-level expression of cloned channels led to the ... kainate receptor channels. Knowledge of the primary structures of Kir channels and the ability to mutate them also has led to ... Expression cloning of the first inward rectifier K channel (Kir) genes provided the necessary break-through that has led to ...
Inward-rectifier potassium channels (Kir, IRK) are a specific subset of potassium channels. To date, seven subfamilies have ... such as the delayed rectifier and A-type potassium channels. Those more "typical" potassium channels preferentially carry ... "Inwardly Recifying Potassium Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and ... Inward-rectifier potassium channel. From Wikipedia, the free encyclopedia. (Redirected from Inward-rectifier potassium ion ...
... channels with distinct biophysical and biochemical properties. Possibly, this diversity reflects the need to regulate and... ... Neurons express a large number of different voltage-gated potassium (Kv) ... Delmas P, Brown DA (2005) Pathways modulating neural KCNQ/M (Kv7) potassium channels. Nat Rev Neurosci 6:850-862 PubMedCrossRef ... Pongs O (1999) Voltage-gated potassium channels: from hyperexcitability to excitement. FEBS Lett 452:31-35 PubMedCrossRefGoogle ...
Mediation of Neuronal Apoptosis by Kv2.1-Encoded Potassium Channels Sumon Pal, Karen A. Hartnett, Jeanne M. Nerbonne, Edwin S. ... Heteromeric KV2/KV8.2 Channels Mediate Delayed Rectifier Potassium Currents in Primate Photoreceptors Jacqueline Gayet-Primo, ... Dysregulation of Kv3.4 Channels in Dorsal Root Ganglia Following Spinal Cord Injury David M. Ritter, Benjamin M. Zemel, Tamara ... Epilepsy-Associated KCNQ2 Channels Regulate Multiple Intrinsic Properties of Layer 2/3 Pyramidal Neurons Zachary Niday, ...
Potassium channels: structures, diseases, and modulators.. Tian C1, Zhu R, Zhu L, Qiu T, Cao Z, Kang T. ... Potassium channels participate in many critical biological functions and play important roles in a variety of diseases. In ... There is no doubt that all these studies on potassium channels as possible pharmaceutical targets will facilitate future ... both qualitative and quantitative approaches are utilized to analyze structural features of modulators of potassium channels. ...
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Mechanism of Voltage Gating in Potassium Channels. By Morten Ø. Jensen, Vishwanath Jogini, David W. Borhani, Abba E. Leffler, ... Mechanism of Voltage Gating in Potassium Channels. By Morten Ø. Jensen, Vishwanath Jogini, David W. Borhani, Abba E. Leffler, ... Using all-atom molecular dynamics simulations, we show how a voltage-gated potassium channel (KV) switches between activated ... We propose a mechanistic model for the sodium/potassium/calcium voltage-gated ion channel superfamily that reconciles ...
Voltage-gated potassium channel (IPR028325)*Potassium channel, voltage dependent, Kv (IPR003968)*Potassium channel, voltage ... GO:0005216 ion channel activity GO:0005249 voltage-gated potassium channel activity GO:0005515 protein binding ... GO:0006813 potassium ion transport GO:0051260 protein homooligomerization GO:0055085 transmembrane transport ...
This domain is found in a variety of potassium channel proteins, including the two membrane helix type ion channels found in ...
Further reports about: , 3D structure , Biozentrum , HCN potassium channels , electrical impulse , potassium channel , ... 3D structure »Biozentrum »HCN potassium channels »electrical impulse »potassium channel »signaling molecule ... These signal-driven potassium channels are also referred to as "pacemaker channels". They help to generate the rhythm of the ... Neurons transmit information with the help of special channels that allow the passage of potassium ions. Defective potassium ...
immunogen = a synthetic peptide corresponding to the C-terminus of human potassium channel Kv4.3 ...
Calcium-activated potassium channels mediate prejunctional inhibition of peripheral sensory nerves. D Stretton, M Miura, M G ... Calcium-activated potassium channels mediate prejunctional inhibition of peripheral sensory nerves. D Stretton, M Miura, M G ... Calcium-activated potassium channels mediate prejunctional inhibition of peripheral sensory nerves. D Stretton, M Miura, M G ... Calcium-activated potassium channels mediate prejunctional inhibition of peripheral sensory nerves Message Subject (Your Name) ...
Renal fibrosis is attenuated by targeted disruption of KCa3.1 potassium channels. Ivica Grgic, Eva Kiss, Brajesh P. Kaistha, ... 1997) A novel gene, hKCa4, encodes the calcium-activated potassium channel in human T lymphocytes. J Biol Chem 272:32723-32726. ... Renal fibrosis is attenuated by targeted disruption of KCa3.1 potassium channels Message Subject (Your Name) has sent you a ... 1996) Potassium channels, proliferation and G1 progression. J Membr Biol 154:91-107. ...
Modulation of Potassium Channels and Arrhythmogenesis. Modulation of K+ channels can have marked effects on the repolarization ... channels. The inward rectifier potassium channel (IK1) was activated by 200-ms test pulses to −100 mV from a holding potential ... Fig 4⇓ summarizes the mean suppressive effects of astemizole and terfenadine on the potassium channels IK, IK1, and Ito in both ... DeFelice LJ, Goolsby WN, Mazzanti M. Potassium channels and the repolarization of cardiac cells. Ann N Y Acad Sci. 1990;588:174 ...
... potassium channels include High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels, ... Profiling Voltage-gated Potassium Channel mRNA Expression in Nigral Neurons using Single-cell RT-PCR Techniques, Optical ... Use of Label-free Optical Biosensors to Detect Modulation of Potassium Channels by G-protein Coupled Receptors, ... Exploring Arterial Smooth Muscle Kv7 Potassium Channel Function using Patch Clamp Electrophysiology and Pressure Myography, ...
Serotonin Receptor Heterogeneity and the Role of Potassium Channels in Neuronal Excitability. ... Serotonin Receptor Heterogeneity and the Role of Potassium Channels in Neuronal Excitability. In: Kito S., Segawa T., Olsen R.W ... channel activation. The mechanism of K+ channel closure is less clear as it is unaffected by PTX or activation of adenylate ... Pertussis toxin-insensitive G protein mediates substance P-induced inhibition of potassium channels in brain neurones, ...
Newly analyzed potassium channel turns out to be a chimeric complex that incorporates the best features of otherwise separately ... a potassium channel combines functions once thought to be invariably asunder. This channel, which is found in common bacteria, ... Potassium ions are attracted from the outside by the high-affinity and high-selective channel-like subunit (KdpA, green), ... Green: channel-like subunit KdpA. Brown: p-type ATPase subunit KdpB. Purple spheres: potassium ions. Pink densities: entrance ...
Potassium channel activator Attenuates salicylate-induced cochlear hearing loss potentially Ameliorating tinnitus. *Sun W ... In this study, we tested whether opening voltage-gated potassium channels using ICA-105665, a novel small molecule that opens ... Sun, W., Liu, J., Zhang, C., Zhou, N., Manohar, S., Miranda, J. A., … Salvi, R. J. (2015). Potassium channel activator ... Therefore, enhancing OHC potassium currents could potentially prevent salicylate-induced temporary hearing loss. ...
Channel activators regulate ATP-sensitive potassium channel (KIR 6.1) expression in chick cardiomyocytes. FEBS Lett. 1997;412: ... The ATP-dependent potassium channels (KATP channels) were originally identified in isolated membrane patches prepared from ... The effects of nucleotides and potassium channel openers on the SUA2A/Kir6.2 complex K+ channel expressed in a mammalian cell ... Molecular cloning of the KATP channel subunit proteins Kir 6.x and SUR have shown that this channel consists of a number of ...
S. B. Long, E. B. Campbell, R. MacKinnon, Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science ... R. F. Service, A new portrait puts potassium pore in a fresh light. Science 309, 867 (2005). [Abstract] [Full Text] ... Forming crystals of the larger, multisubunit eukaryotic K+ channels has been more challenging, but Long et al. (see the cover ... Voltage-gated K+ channels open in response to cell depolarization, reacting to the change in potential by movement of four ...
  • The molecular nature of this important current has yet to be established, but in this study, we provide strong evidence to suggest that IK SO is the functional correlate of the recently identified two-pore domain potassium channel TASK-1. (wright.edu)
  • We hypothesize that HFD causes an upregulation of 2-pore domain potassium channels, resulting in hyperpolarization of nodose ganglia (NG) and decreased vagal response to satiety signals, which contribute to hyperphagia. (jci.org)
  • We show that a 2-week HFD caused an upregulation of 2-pore domain TWIK-related spinal cord K+ (TRESK) and TWIK-related acid-sensitive K+ 1 (TASK1) channels by 330% ± 50% and 60% ± 20%, respectively, in NG. (jci.org)
  • A Functional Role for the Two-Pore Domain Potassium Channel TASK-1 in " by Julie A. Millar, Lynne Barratt et al. (wright.edu)
  • When the signaling molecule cAMP docks onto the potassium channel, it causes a rearrangement and shift in the protein scaffold," explains Julia Kowal, first author of this study. (innovations-report.com)
  • Data from the hippocampus and DRN indicate the 5-HT induced hyperpolarisation to be sensitive to Pertussis Toxin (PTX) and irreversibly mimicked by GTPγS, a non-hydrolysable analogue of GTP, suggesting the involvement of a G protein in K + channel activation. (springer.com)
  • These results suggest that the cardiac K ATP channel protein possesses endogenous cytoprotective properties when transfected into a noncardiac cell type. (ahajournals.org)
  • A paper on this work has been published in Journal of Neuroscience on 2010 August 4: Fragile X mental retardation protein is required for rapid experience-dependent regulation of the potassium channel Kv3.1b by Leonard Kaczmarek, PhD and Jack Kronengold, PhD Our laboratory has investigated how the excitability of neurons becomes modified in the absence of the FMRP protein. (fraxa.org)
  • We have found that the levels of two potassium channels, termed Slack and Kv3.1 are altered in mice that lack this protein. (fraxa.org)
  • With a $282,000 funding from FRAXA Research Foundation, Dr. Leonard Kaczmarek and colleagues explored association of Slack channels with the Fragile X protein (FMRP). (fraxa.org)
  • Each Potassium Channel Kv3.1 Peptide and Potassium Channel Kv3.1 Protein is fully covered by our Guarantee+, to give you complete peace of mind and the support when you need it. (novusbio.com)
  • TBK1 activity regulates binding of the channel with Hax-1, an anti-apoptotic protein required for survival of cerebellar neurons, and that embeds Kv3.3 in a stable actin cytoskeleton at the plasma membrane. (ssrn.com)
  • Cells that express the mutant channel have increased internalization of Hax-1 and accumulate multivesicular bodies containing this cell survival protein, coupled to depolarization-induced loss of the channels themselves. (ssrn.com)
  • Our studies indicate that the activation of Kv3.3 channels is linked directly to TBK1 activity and channel mutations enhance internalization of the cell survival protein Hax-1 to which they are bound. (ssrn.com)
  • It is postulated that the precursor channel protein resembled the pore module of modern K + channels ( Fig. 1A ). (plantphysiol.org)
  • In this brief review, we suggest that a viral-encoded K + protein might be the evolutionary ancestor of all K + channel proteins. (plantphysiol.org)
  • GIRK channels (short for G-protein-coupled inwardly rectifying potassium channels) a subtype of the many different potassium channels in the brain are widely distributed in the brain and regulate neuron-to-neuron communication. (bio-medicine.org)
  • U-0126, the mitogen-activated protein kinase inhibitors, could reverse macrophage migration induced by Kv1.3 channel overexpression. (sigmaaldrich.com)
  • Instead, as these TRP ion channels do not require other parts of the protein to move in order to open the channel, they can be activated by their own inherent sensitivity to heat. (elifesciences.org)
  • Activation of ion channels in turn is the result of complex conformational rearrangements in channel protein controlled by specific physical or chemical stimuli ( Hille, 2001 ). (elifesciences.org)
  • Expression of the minK protein is associated with potassium channel activity in a variety of tissues ( Busch and Suessbrich, 1997 ). (rupress.org)
  • Abstract The ATP-sensitive potassium channels (K ATP ) are activated either by a decrease in intracellular ATP content or by a lowering of the ATP-ADP ratio such as during stroke. (ahajournals.org)
  • Abstract -Potassium ion (K + ) channel activity is a major regulator of vascular muscle cell membrane potential ( E m ) and is therefore an important determinant of vascular tone. (ahajournals.org)
  • Browne DL, Gancher ST, Nutt JG, Brunt ERP, Smith EA, Kramer P, Litt M (1994) Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene KCNA1. (springer.com)
  • In Potassium Channels: Methods and Protocols , experts in the field present a range of experimental approaches that have been developed to investigate potassium channel structure, function, pharmacology, cell biology, gene expression, and their role in disease. (springer.com)
  • There is genetic evidence that the plethora of K + channels results from several major genetic events, such as gene fusions and gene duplications ( Anderson and Greenberg, 2001 ). (plantphysiol.org)
  • The tandem architecture of the TWIK channels, with the tandem 2TM structure (2*2TM) structure, probably occurred after a gene duplication of the pore module. (plantphysiol.org)
  • Gene fusion of the precursor to the latter could explain the structure of the TOK channel in which the 2TM motive and the 6TM motive are combined (6+2TM). (plantphysiol.org)
  • As further progress is made in the development of more selective drugs and through molecular approaches such as gene targeting technology in mice, specific K + channel abnormalities and their causes in particular diseases should be more readily identified, providing novel directions for vascular therapy. (ahajournals.org)
  • A more recent study found that at moderate concentrations (0.1-1 mM), salicylate also causes a concentration-dependent reversible reduction of a voltage-gated potassium channel, which is encoded by KCNQ4 gene of OHCs ( 10 ). (frontiersin.org)
  • The human ether-a-go-go-related gene (hERG) encodes channels mediating the rapid delayed rectifier K+ current (IKr). (bl.uk)
  • Genomic organization, nucleotide sequence, and cellular distribution of a Shaw-related potassium channel gene, Kv3.3, and mapping of Kv3.3 and Kv3.4 to human chromosomes 19 and 1. (wikigenes.org)
  • When coexpressed with the minK gene product, a slowly activating and much larger potassium current results. (rupress.org)
  • The other partner in the I Ks channel is the product of the LQT1 gene. (rupress.org)
  • This suggests that ChTX-sensitive K(+)-channel activation may be a common mechanism for the prejunctional modulation of sensory nerves in airways. (pnas.org)
  • Since potassium channels are intrinsically involved in repolarization, this study was designed to evaluate the effect of the nonsedating antihistamines on potassium channel modulation. (ahajournals.org)
  • The effects of extracellular acidosis on IhERG kinetics were preserved when the shortened hERG I b isoform was studied, indicating that a full-length N-terminus is not necessary for acidic modulation of hERG channel function. (bl.uk)
  • Episodic ataxia type 1 (EA-1) is an autosomal dominant neurological disorder caused by mutations in the potassium channel Kv1.1. (curehunter.com)
  • Evidence is presented that the decrease in 5-HT2CR editing is caused by down-regulation of adenosine deaminase ADAR2 and that editing of at least one other ADAR2 target, potassium channel Kv1.1, is decreased after SCI. (curehunter.com)
  • Studies at Yale University and elsewhere are showing that FMRP plays a significant role in the regulation of potassium channels. (fraxa.org)
  • Cooper EC, Milroy A, Jan YN, Jan LY, Lowenstein DH (1998) Presynaptic localization of Kv1.4-containing A-type potassium channels near excitatory synapses in the hippocampus. (springer.com)
  • Diochot S, Schweitz H, Béress L, Lazdunski M (1998) Sea anemone peptides with a specific blocking activity against the fast inactivating potassium channel Kv3.4. (springer.com)
  • see the cover and the news story by Service) now present in two papers a 2.9-angstrom-resolution crystal structure and a mechanistic analysis for eukaryotic Kv1.2 channels from the Shaker family. (sciencemag.org)
  • Prof. Henning Stahlberg's team at the Biozentrum of the University of Basel has now elucidated the full structure of a bacterial counterpart of this type of potassium channel, which has provided new insights into its functioning. (innovations-report.com)
  • This observation raises the possibility that ion channels other than Kv1.3, such as KCa3.1, may have functional activity. (nature.com)
  • Complementary DNAs representing three voltage-gated K(+) channels from humans (HuKI, HuKII, and HuKIV) were isolated, their nucleotide sequences determined, and their functional products examined electrophysiologically. (nih.gov)
  • Here, we examined the localization, native interactions, and functional properties of K V 8.2-containing channels in mouse, macaque, and human photoreceptors of either sex. (jneurosci.org)
  • The pore module, which consists of two transmembrane domains connected by a pore helix containing the canonical filter sequence of K + channels, assembles into a functional tetramer. (plantphysiol.org)
  • 1 2 3 4 5 6 This Brief Review will first provide a short description of the functional characteristics of the 4 main types of vascular K + channels and the likely physiological importance of these channels, as well as the phenomenon of K + channel-mediated, endothelium-dependent vascular hyperpolarization. (ahajournals.org)
  • Coupling of conformational changes in one domain to another provides the basis for transducing voltage and ligand binding into channel opening and, therefore, defines, together with the functional properties of the gate and sensors, the signal transduction properties of the channel. (rupress.org)
  • B) Schematic organization of functional domains in the tetrameric channel. (rupress.org)
  • Potassium channel activator Atten. (mendeley.com)
  • The present invention describes novel nitrosated and/or nitrosylated potassium channel activators, and novel compositions comprising at least one nitrosated and/or nitrosylated potassium channel activator, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates. (google.com)
  • The present invention describes novel nitrosated and/or nitrosylated potassium channel activators, and novel compositions comprising at least one nitrosated and/or nitrosylated potassium channel activator, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one vasoactive agent. (google.com)
  • Voltage-gated Kv1.3 and Ca 2+ -dependent KCa3.1 are the most prevalent K + channels expressed by human and rat T cells. (nature.com)
  • However, experiments with Kv1.3 KO rats and Kv1.3 siRNA knockdown or channel-specific inhibition of human T cells show that maximal T-cell responses against autoantigen or repeated tetanus toxoid stimulations require both Kv1.3 and KCa3.1. (nature.com)
  • Cui J, Aldrich RW (2000) Allosteric linkage between voltage and Ca 2+ -dependent activation of BK-type mslo1 K + channels. (springer.com)
  • Patch-clamp studies of microglial cells showed that these cells express a wide variety of potassium channels. (frontiersin.org)
  • In humans, the good news is that an FDA-approved drug, retigabine works by "opening" the Kv7 channel. (mdanderson.org)
  • Looking forward, potassium channel opener drugs could rescue some symptoms of Fragile X in humans. (fraxa.org)
  • The role of NO in the regulation of the mechanical properties of conduit arteries is controversial in humans, and the involvement of an endothelium-derived hyperpolarizing factor (EDHF), acting through calcium-activated potassium (K Ca ) channels, has never been investigated at this level in vivo. (ahajournals.org)
  • 2,4 Whether an increase in vascular calcium-activated potassium (K Ca ) channel activity after NO synthesis inhibition could contribute to the maintenance of basal conduit artery diameter and mechanics has never been investigated in vivo in humans. (ahajournals.org)
  • 12,13 In humans, the recent demonstration of the contribution of K Ca channels in the regulation of forearm arteriolar resistance strongly suggests a role for EDHF in vivo. (ahajournals.org)
  • The present analysis of kcne3-/- mice strongly supports a crucial role of KCNQ1/KCNE3 channels in salt- and fluid secretion across intestinal and airway epithelia. (hu-berlin.de)
  • KCNQ1 through KCNQ5, and KCNQ channel has six transmembrane domains and a single pore loop ( 11 ). (frontiersin.org)