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)

Alternative sulfonylurea receptor expression defines metabolic sensitivity of K-ATP channels in dopaminergic midbrain neurons. (1/2415)

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. (2/2415)

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)

Inducible genetic suppression of neuronal excitability. (3/2415)

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)

Glucose-receptive neurones in the rat ventromedial hypothalamus express KATP channels composed of Kir6.1 and SUR1 subunits. (4/2415)

1. Patch-clamp recordings were made from rat ventromedial hypothalamic neurones in slices of brain tissue in vitro. In cell-attached recordings, removal of extracellular glucose or metabolic inhibition with sodium azide reduced the firing rate of a subpopulation of cells through the activation of a 65 pS channel that was blocked by the sulphonylureas tolbutamide and glibenclamide. 2. In whole-cell patch-clamp recordings, in the absence of ATP in the electrode solution, glucose-receptive neurones gradually hyperpolarized due to the induction of an outward current at -60 mV. This outward current and the resultant hyperpolarization were blocked by the sulphonylureas tolbutamide and glibenclamide. 3. In recordings where the electrode solution contained 4 mM ATP, this outward current was not observed. Under these conditions, 500 microM diazoxide was found to induce an outward current that was blocked by tolbutamide. 4. In cell-attached recordings diazoxide and the active fragment of leptin (leptin 22-56) reduced the firing rate of glucose-receptive neurones by the activation of a channel with similar properties to that induced by removal of extracellular glucose. 5. Reverse transcription followed by the polymerase chain reaction using cytoplasm from single glucose-receptive neurones demonstrated the expression of the ATP-sensitive potassium (KATP) channel subunits Kir6.1 and SUR1 but not Kir6.2 or SUR2. 6. It is concluded that glucose-receptive neurones within the rat ventromedial hypothalamus exhibit a KATP channel current with pharmacological and molecular properties similar to those reported in other tissues.  (+info)

Somatostatin induces hyperpolarization in pancreatic islet alpha cells by activating a G protein-gated K+ channel. (5/2415)

Somatostatin inhibits glucagon-secretion from pancreatic alpha cells but its underlying mechanism is unknown. In mouse alpha cells, we found that somatostatin induced prominent hyperpolarization by activating a K+ channel, which was unaffected by tolbutamide but prevented by pre-treating the cells with pertussis toxin. The K+ channel was activated by intracellular GTP (with somatostatin), GTPgammaS or Gbetagamma subunits. It was thus identified as a G protein-gated K+ (K(G)) channel. RT-PCR and immunohistochemical analyses suggested the K(G) channel to be composed of Kir3.2c and Kir3.4. This study identified a novel ionic mechanism involved in somatostatin-inhibition of glucagon-secretion from pancreatic alpha cells.  (+info)

Proadrenomedullin N-terminal 20 peptide hyperpolarizes the membrane by activating an inwardly rectifying K+ current in differentiated PC12 cells. (6/2415)

The mechanism of proadrenomedullin N-terminal 20 peptide (PAMP)-induced inhibition of catecholamine release from adrenergic nerve was investigated in nerve growth factor-treated PC12 cells that have differentiated characteristics somewhat similar to noradrenergic neurons. The effect of PAMP on the excitability of these cells was investigated with the use of perforated whole-cell clamp. PAMP hyperpolarized the membrane by increasing a K+ conductance in a dose-dependent manner. The current-voltage relationship (I-V) relationship of the PAMP-induced K+ conductance exhibited inward-going rectification. The activation was abolished by microinjecting GDPbetaS into the cells or pretreating the cells with pertussis toxin. These results indicate that a pertussis toxin-sensitive G protein is involved in the signal transduction. The PAMP-induced activation of the K+ conductance was attenuated by microinjecting antibody against the carboxyl terminus of Galphai3, but it was not influenced by microinjecting antibody against the common carboxyl termini of Galphai1 and Galphai2, which indicated that the G protein coupling the PAMP receptor to the inwardly rectifying K+ current is Galphai3. The PAMP-induced hyperpolarization may inhibit the catecholamine release from the neurons by attenuating the action potential frequency.  (+info)

Selective activation of heterologously expressed G protein-gated K+ channels by M2 muscarinic receptors in rat sympathetic neurones. (7/2415)

1. G protein-regulated inward rectifier K+ (GIRK) channels were over-expressed in dissociated rat superior cervical sympathetic (SCG) neurones by co-transfecting green fluorescent protein (GFP)-, GIRK1- and GIRK2-expressing plasmids using the biolistic technique. Membrane currents were subsequently recorded with whole-cell patch electrodes. 2. Co-transfected cells had larger Ba2+-sensitive inwardly rectifying currents and 13 mV more negative resting potentials (in 3 mM [K+]o) than non-transfected cells, or cells transfected with GIRK1 or GIRK2 alone. 3. Carbachol (CCh, 1-30 microM) increased the inwardly rectifying current in 70 % of GIRK1+ GIRK2-transfected cells by 261 +/- 53 % (n = 6, CCh 30 microM) at -120 mV, but had no effect in non-transfected cells or in cells transfected with GIRK1 or GIRK2 alone. Pertussis toxin prevented the effect of carbachol but had no effect on basal currents. 4. The effect of CCh was antagonized by 6 nM tripitramine but not by 100 nM pirenzepine, consistent with activation of endogenous M2 muscarinic acetylcholine receptors. 5. In contrast, inhibition of the voltage-activated Ca2+ current by CCh was antagonized by 100 nM pirenzepine but not by 6 nM tripitramine, indicating that it was mediated by M4 muscarinic acetylcholine receptors. 6. We conclude that endogenous M2 and M4 muscarinic receptors selectively couple to GIRK currents and Ca2+ currents respectively, with negligible cross-talk.  (+info)

Kir2.1 encodes the inward rectifier potassium channel in rat arterial smooth muscle cells. (8/2415)

1. The molecular nature of the strong inward rectifier K+ channel in vascular smooth muscle was explored by using isolated cell RT-PCR, cDNA cloning and expression techniques. 2. RT-PCR of RNA from single smooth muscle cells of rat cerebral (basilar), coronary and mesenteric arteries revealed transcripts for Kir2.1. Transcripts for Kir2.2 and Kir2.3 were not found. 3. Quantitative PCR analysis revealed significant differences in transcript levels of Kir2.1 between the different vascular preparations (n = 3; P < 0.05). A two-fold difference was detected between Kir2.1 mRNA and beta-actin mRNA in coronary arteries when compared with relative levels measured in mesenteric and basilar preparations. 4. Kir2.1 was cloned from rat mesenteric vascular smooth muscle cells and expressed in Xenopus oocytes. Currents were strongly inwardly rectifying and selective for K+. 5. The effect of extracellular Ba2+, Ca2+, Mg2+ and Cs2+ ions on cloned Kir2.1 channels expressed in Xenopus oocytes was examined. Ba2+ and Cs+ block were steeply voltage dependent, whereas block by external Ca2+ and Mg2+ exhibited little voltage dependence. The apparent half-block constants and voltage dependences for Ba2+, Cs+, Ca2+ and Mg2+ were very similar for inward rectifier K+ currents from native cells and cloned Kir2.1 channels expressed in oocytes. 6. Molecular studies demonstrate that Kir2.1 is the only member of the Kir2 channel subfamily present in vascular arterial smooth muscle cells. Expression of cloned Kir2.1 in Xenopus oocytes resulted in inward rectifier K+ currents that strongly resemble those that are observed in native vascular arterial smooth muscle cells. We conclude that Kir2.1 encodes for inward rectifier K+ channels in arterial smooth muscle.  (+info)

Inward-rectifier potassium channels (Kir, IRK) are a specific subset of potassium channels. To date, seven subfamilies have been identified in various mammalian cell types, plants, and bacteria. They are the targets of multiple toxins, and malfunction of the channels has been implicated in several diseases. IRK channels possess a pore domain, homologous to that of voltage-gated ion channels, and flanking transmembrane segments (TMSs). They may exist in the membrane as homo- or heterooligomers and each monomer possesses between 2 and 4 TMSs. In terms of function, these proteins transport potassium (K+), with a greater tendency for K+ uptake than K+ export. A channel that is "inwardly-rectifying" is one that passes current (positive charge) more easily in the inward direction (into the cell) than in the outward direction (out of the cell). It is thought that this current may play an important role in regulating neuronal activity, by helping to stabilize the resting membrane potential of the cell. ...
TY - JOUR. T1 - Compound-induced block of ion channel pore function. T2 - Inward-rectifier potassium channels as a model. AU - Furutani, Kazuharu. AU - Hibino, Hiroshi. AU - Inanobe, Atsushi. AU - Kurachi, Yoshihisa. PY - 2009/12/1. Y1 - 2009/12/1. N2 - Small chemical compounds modulate ion channel functions. This is the reflection of ligand interactions with ion channels at their various sites. Many biophysical and biochemical researches have been performed on this subject and have provided important basic concepts on the structure-functional relationships of ion channels. Especially, ion channel blockers have been excellent tools for biophysical studies of ion channels and some of them are actually used for treating various diseases. The mechanisms underlying the blocking action of various chemical compounds, however, remain largely unknown at the atomic level, partly because of the promiscuous nature of the reaction. As one of the attempts to overcome the problem, we have adopted a novel ...
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).
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).
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 ...
Since the mechanism of salt impairing NO-induced vascular relaxation is not fully clear, this study was designed to investigate the role of potassium (K+) channels in the vasodilatory effects of NO donor in salt loaded rats. Isolated thoracic aortic rings of adult male albino rats fed 8% NaCl containing diet for six weeks were used for isometric tension recording using PowerLab tissue bath system. The recorded data revealed that high salt diet (HS) did not change the relaxation responses to sodium nitroprusside (SNP, an NO donor) in rats thoracic aortic rings. SNP-induced relaxation in salt loaded rats was significantly lower in rings contracted by high K+ than phenylephrine (PE, a selective α1-adrenergic receptor agonist). On the other hand, incubation of aortic rings from salt loaded rats with inward-rectifier K+ (KIR) channel blockers either individually or simultaneously with other K+ channel blockers significantly inhibited SNP-induced relaxation in PE-contracted rings; however incubation ...
A channel that is "inwardly-rectifying" is one that passes current (positive charge) more easily in the inward direction (into the cell) than in the outward direction (out of the cell). It is thought that this current may play an important role in regulating neuronal activity, by helping to stabilize the resting membrane potential of the cell. By convention, inward current (positive charge moving into the cell) is displayed in voltage clamp as a downward deflection, while an outward current (positive charge moving out of the cell) is shown as an upward deflection. At membrane potentials negative to potassiums reversal potential, inwardly rectifying K+ channels support the flow of positively charged K+ ions into the cell, pushing the membrane potential back to the resting potential. This can be seen in figure 1: when the membrane potential is clamped negative to the channels resting potential (e.g. -60 mV), inward current flows (i.e. positive charge flows into the cell). However, when the ...
A channel that is "inwardly-rectifying" is one that passes current (positive charge) more easily in the inward direction (into the cell) than in the outward direction (out of the cell). It is thought that this current may play an important role in regulating neuronal activity, by helping to stabilize the resting membrane potential of the cell. By convention, inward current (positive charge moving into the cell) is displayed in voltage clamp as a downward deflection, while an outward current (positive charge moving out of the cell) is shown as an upward deflection. At membrane potentials negative to potassiums reversal potential, inwardly rectifying K+ channels support the flow of positively charged K+ ions into the cell, pushing the membrane potential back to the resting potential. This can be seen in figure 1: when the membrane potential is clamped negative to the channels resting potential (e.g. -60 mV), inward current flows (i.e. positive charge flows into the cell). However, when the ...
We demonstrate that tamoxifen, a synthetic nonsteroidal triphenylethylene derivative, which has estrogenic, antiestrogenic effects, 4-hydroxytamoxifen, an active metabolite of tamoxifen, and raloxifene, the selective estrogen receptor modulator used to treat osteoporosis in postmenopausal women, inhibit the strong inward rectifier potassium channels Kir2.x. The order of inhibition for all three drugs was Kir2.3 , Kir2.1 ∼ Kir2.2. The inhibition of Kir2.x current by tamoxifen, 4-hydroxytamoxifen, and raloxifene occurred slowly (T1/2 ∼ 6 min), and the currents only partially recovered after washout (∼30%). Tamoxifen also inhibited IK1 in cat atrial and ventricular myocytes, and the effects were greater in the former than the latter.. The inhibition induced by tamoxifen, 4-hydroxytamoxifen, and raloxifene was concentration-dependent but voltage-independent. The potency of tamoxifen to inhibit Kir2.1 channel was greater than 4-hydroxytamoxifen and raloxifene. The IC50 of inhibition by ...
Heteromultimerization between different potassium channel subunits can generate channels with novel functional properties and thus contributes to the rich functional diversity of this gene family. The inwardly rectifying potassium channel subunit Kir5.1 exhibits highly selective heteromultimerization with Kir4.1 to generate heteromeric Kir4.1/Kir5.1 channels with unique rectification and kinetic properties. These novel channels are also inhibited by intracellular pH within the physiological range and are thought to play a key role in linking K+ and H+ homeostasis by the kidney. However, the mechanisms that control heteromeric K+ channel assembly and the structural elements that generate their unique functional properties are poorly understood. In this study we identify residues at an intersubunit interface between the cytoplasmic domains of Kir5.1 and Kir4.1 that influence the novel rectification and gating properties of heteromeric Kir4.1/Kir5.1 channels and that also contribute to their pH sensitivity
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 ...
ATP-sensitive potassium channels (KATP) regulate a range of biological activities by coupling membrane excitability to the cellular metabolic state. In particular, it has been proposed that KATP channels and specifically, the channel subunits Kir6.1 and SUR2B, play an important role in the regulation of vascular tone. However, recent experiments have suggested that KATP channels outside the vascular smooth muscle compartment are the key determinant of the observed behavior. Thus, we address the importance of the vascular smooth muscle KATP channel, using a novel murine model in which it is possible to conditionally delete the Kir6.1 subunit. Using a combination of molecular, electrophysiological, in vitro, and in vivo techniques, we confirmed the absence of Kir6.1 and KATP currents and responses specifically in smooth muscle. Mice with conditional deletion of Kir6.1 showed no obvious arrhythmic phenotype even after provocation with ergonovine. However, these mice were hypertensive and vascular ...
ATP-sensitive K(+) (K(ATP)) channels, comprised of pore-forming Kir6.x and regulatory SURx subunits, play important roles in many cellular functions; because of their sensitivity to inhibition by intracellular ATP, K(ATP) channels provide a link between cell metabolism and membrane electrical activity. We constructed structural homology models of Kir6.2 and a series of Kir6.2 channels carrying mutations within the putative ATP-binding site. Computational docking was carried out to determine the conformation of ATP in its binding site. The Linear Interaction Energy (LIE) method was used to estimate the free-energy of ATP binding to wild-type and mutant Kir6.2 channels. Comparisons of the theoretical binding free energies for ATP with those determined from mutational experiments enabled the identification of the most probable conformation of ATP bound to the Kir6.2 channel. A set of LIE parameters was defined that may enable prediction of the effects of additional Kir6.2 mutations within the ATP binding
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
1. ATP-sensitive potassium (KATP) channels are composed of pore-forming Kir6.2 and regulatory SUR subunits. A truncated isoform of Kir6.2, Kir6.2DeltaC26, forms ATP-sensitive channels in the absence of SUR1, suggesting the ATP-inhibitory site lies on Kir6.2. 2. Previous studies have shown that mutation of the lysine residue at position 185 (K185) in the C-terminus of Kir6.2 to glutamine, decreased the channel sensitivity to ATP without affecting the single-channel conductance or the intrinsic channel kinetics. This mutation also impaired 8-azido[32P]-ATP binding to Kir6.2. 3. To determine if K185 interacts directly with ATP, we made a range of mutations at this position, and examined the effect on the channel ATP sensitivity by recording macroscopic currents in membrane patches excised from Xenopus oocytes expressing wild-type or mutant Kir6.2DeltaC26. 4. Substitution of K185 by a positively charged amino acid (arginine) had no substantial effect on the sensitivity of the channel to ATP. Mutation to a
MS Model, Version 5.0 ********************** //*************************** MScell.p ********************** // Tom Sheehan [email protected] [email protected] 703-538-836 //***************************************************************************** *relative *cartesian *asymmetric *lambda_warn *set_global ELEAK -0.070 //*set_global RA 1.0 //*set_global RM 8.695652 1.8 1.83-0.0295 1.86-0.029 1.96-0.0275 2.16-0.025 *set_global RM 1.8 //1.8-0.03 //*set_global CM 0.010 //change Cm to account for no spines - make 3x higher? 0.03 0.025 *set_global CM 0.03 *set_global EREST_ACT -0.085 *start_cell /library/tert_dend tert_dend none 35.927 0 0 0.80 tert_dend2 . 35.927 0 0 0.80 tert_dend3 . 35.927 0 0 0.80 tert_dend4 . 35.927 0 0 0.80 tert_dend5 . 35.927 0 0 0.80 tert_dend6 . 35.927 0 0 0.80 tert_dend7 . 35.927 0 0 0.80 tert_dend8 . 35.927 0 0 0.80 tert_dend9 . 35.927 0 0 0.80 tert_dend10 . 35.927 0 0 0.80 tert_dend11 . 35.927 0 0 0.80 *makeproto /library/tert_dend *start_cell /library/sec_dend sec_dend none ...
from neuron import h import matplotlib.pyplot as plt import numpy as np import seaborn as sns soma = h.Section() dend = h.Section() soma.L = 10 soma.diam = 10 soma.Ra = 1000 soma.insert(pas) soma.g_pas = 1e-5 soma.cm = 1 dend.L = 200 dend.nseg = 47 dend.diam = 3 dend.Ra = 1000 dend.insert(pas) dend.g_pas = 1e-3 dend.cm = 1 dend.connect(soma(0), 0) # dend.connect(soma(0), 1) istim = h.IClamp(1.0, dend) istim.amp = 0.2 istim.delay = 100 istim.dur = 30 vdlist = [] vdlist.append(h.Vector()) vdlist.append(h.Vector()) vdlist.append(h.Vector()) vs = h.Vector() t = h.Vector() vdlist[0].record(dend(1.0)._ref_v) vdlist[1].record(dend(0.5)._ref_v) vdlist[2].record(dend(0.0)._ref_v) vs.record(soma(0.5)._ref_v) t.record(h._ref_t) h.load_file("stdrun.hoc") h.init() h.tstop = 200 h.run() # Plotting code from here rows = 2 fig = plt.figure(); plot_num = 1; ax2 = fig.add_subplot(rows, 1, plot_num); plot_num += 1; ax2.set_ylabel(Vd) ax2.set_xlabel(t) ax2.xaxis.set_ticks(np.arange(0, h.tstop, 10)) ...
Anionic phospholipids (e.g. PIP2) activate all inward rectifier K+ (Kir) channels and degradation of phospholipids by endogenous lipid phosphatases or phospholipases is a well-accepted mechanism for Kir current rundown in excised membrane patches. The rate of Kir current rundown varies and is inversely correlated to the PIP-binding affinity of the channel being studied, with rundown being faster for channels that bind PIPs less strongly [14-16].. Sensitivity of KATP channels to phosphoinositide turnover was first demonstrated in giant membrane patches from cardiac myocytes, where native Kir6.2/SUR2A channels are abundant [17]. These channels run down rapidly in excised patches exposed to nucleotide-free solutions, but following exposure to intracellular MgATP their activity is (at least partially) restored, as seen by comparing the current in control solution before and after ATP application. This increase in channel activity was mimicked by intracellular application of PIP2, and reversed by ...
KATP channels are unique amongst known potassium channels in requiring an unrelated ABC protein subunit (SUR1) in addition to an inward rectifier K channel (Kir6.2) subunit (Inagaki et al., 1995a). In other cloned inward rectifiers, strong inward rectification is controlled by a pore-lining residue in the M2 transmembrane segment (Fakler et al., 1994; Ficker et al., 1994; Lopatin et al., 1994; Lu and MacKinnon, 1994; Stanfield et al., 1994). Mutation of the corresponding residue in Kir6.2 from asparagine to aspartate results in generation of KATP channels that rectify strongly in the presence of cytoplasmic spermine (Fig. 1 b; Clement et al., 1997; Shyng et al., 1997), single channel conductance being unaltered and channels remaining sensitive to inhibition by ATP (Shyng et al., 1997). The requirement for SUR1 to form active channels still raises the possibility that the receptor might also contribute to the pore, and perhaps reduce or otherwise alter the number of Kir6.2 subunits involved. The ...
from simpleNrnLib import * def simpleComputational(): dend = make_section("dend") dend.L = 1000 dend.diam = 10 dend.nseg = 21 dend.insert(pas) soma = make_section("soma") soma.L = 1000 soma.diam = 10 soma.nseg = 21 soma.insert(pas) soma.connect(dend,1,0) # connect dend(1) to soma(0) for sec in h.allsec(): sec.Ra = 200 sec.cm = 5.001 for seg in sec: seg.pas.g = 5e-5 seg.pas.e = 0 iClamp = make_iClamp(dend(0)) iClamp.delay = 10 iClamp.amp = 1.2 iClamp.dur = 500000 voltage = h.RangeVarPlot("v") voltage.begin(0) voltage.end(1) tstop = 5000 v_init = -60 h.dt = 0.025 h.finitialize(v_init) h.fcurrent() run(tstop) vVec = h.Vector() pVec = h.Vector() voltage.to_vector(vVec,pVec) return pVec, ...
Morphology file for Golgi cell // A single compartment neuron with a spherical soma yielding // an Rin (78 MegaOhm) and a time-constant (24 msec) as tabulated in Midtgaard (1992). // The resulting Cm is 0.31 nF, assuming a specific membrane capacitance of 0.01 (F/m^2). // The resulting surface area is 0.31e5 um^2. // Written by RM (27/11/95). // changed /library/soma to /library/interneuron/soma on 16/4/96 MAEX *relative *set_compt_param ELEAK {ELEAK} *set_compt_param EREST_ACT {EREST_ACT} *set_compt_param RM 3.03 // 2.4000 // 24 000 ohm.cm^2 *set_compt_param RA 1.0000 // *set_compt_param CM 0.0100 // 1microF/cm^2 // The entire neuron has now about the same membrane surface area // as the original single soma compartment. In addition, all // compartments have the same area. *compt /library/granule/soma soma none 0.000 0.000 0.000 12.25 // 30.0 // 99.33 *compt /library/granule/dend dend[0] soma 0.0 15.0 0.0 5.0 dend[1] dend[0] 0.0 15.0 0.0 5.0 dend[2] dend[1] 0.0 18.75 0.0 4.0 dend[3] dend[2] 0.0 ...
Inwardly rectifying potassium (Kir) channels form gates in the cell membrane that regulate the flow of K(+) ions into and out of the cell, thereby influencing the membrane potential and electrical signaling of many cell types, including neurons and cardiomyocytes. Kir-channel function depends on other cellular proteins that aid in the folding of channel subunits, assembly into tetrameric complexes, trafficking of quality-controlled channels to the plasma membrane, and regulation of channel activity at the cell surface. We used the yeast Saccharomyces cerevisiae as a model system to identify proteins necessary for the functional expression of a mammalian Kir channel at the cell surface. A screen of 376 yeast strains, each lacking one nonessential protein localized to the early secretory pathway, identified seven deletion strains in which functional expression of the Kir channel at the plasma membrane was impaired. Six deletions were of genes with known functions in trafficking and lipid ...
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In HAECs, the molecular diversity of Kir2 subunits at the transcript level is higher than the diversity of functional Kir. While for Kir2.3 this discrepancy could be explained by undetectable levels of protein expression due to very low transcription, the transcript level of Kir2.4 is similar to that of Kir2.1, suggesting that Kir2.4 functional expression is regulated at a posttranscriptional level. A discrepancy between the heterogeneity of K+ channels at the transcript and functional levels was reported previously for Kir2.x channels in human myoblasts (8) and for voltage-gated K+ channels in rat cardiomyocytes (2, 49), and it has been proposed that translational-posttranslational steps may contribute a rate-limiting step to channel expression (38). Protein expression of Kir2.x subunits in HAECs is consistent with the functional expression of the channels.. The peak IK unitary conductance levels in HAECs (25 and 35 pS) are similar to previously reported values in human umbilical vein ...
HEK293-HuCACNA1C/NEUROD1/CACNA2D1/KCNJ2 cell line is a hypotriploid human cell line, which has been transfected with a human calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C), a human neuronal differentiation 1 (NEUROD1), a human calcium channel, voltage-dependent, alpha 2/delta subunit 1 (CACNA2D1) and a human potassium inwardly-rectifying channel, subfamily J, member 2 (KCNJ2) to allow stably express of the human CACNA1C, NEUROD1, CACNA2D1 and KCNJ2. It is an example of a cell line tr
The present study concludes on the basis of independent kinetic and pharmacological evidence that two components of IK are present in canine atrial and ventricular myocytes. Two tail current components can be distinguished kinetically on the basis of (1) two exponential components describing IK deactivation, (2) differences in the voltage and time dependence of activation of each tail component, and (3) the differential sensitivity of each component to reduced [K+]o. IK components described kinetically (IKe1 and IKe2) were subsequently compared with components identified pharmacologically by using E-4031. The voltage dependence, activation kinetics, and rectification properties of E-4031-sensitive current (typically defined as IKr) were analogous to IKe2 (defined kinetically), whereas E-4031-insensitive current (IKs) was analogous to the more rapid IKe1 in atrial and ventricular myocytes. These similarities argue against the possibility that pharmacologically defined deactivation of IKr is ...
Effects of PPIs on ATP sensitivity at the single-channel level. Single-channel KATP current recorded in an inside-out patch at 0 mV from a rat ventricular cell
Դիգոքսինի ազդեցության հիմնական մեխանիզմը ներառում է սրտամկանում նատրիում/կալիումական ադենոզին եռֆոսֆատազի ( Na + / K + ATPազ) արգելակումը: Այս արգելակումը հանգեցնում է ներբջջային նատրիումի մակարդակի բարձրացմանը, ինչը հետևանք է նատրիումի-կալցիումի փոխարկիչի ակտիվության նվազեցման, որը սովորաբար բջջի մեջ ներմուծում է նատրիումի երեք իոն եւ բջջից դուրս տեղափոխում կալցիումի մեկ իոն: Այս փոխարկիչի անգործությունը առաջացնում է ներբջջային կալցիումի կոնցենտրացիայի ավելացում, որը հասանելի է կծկում առաջացնող սպիտակուցներին: Կալցիումի բարձր մակարդակը ...
Andersen-Tawil Syndrome is a genetic condition that causes periods of muscle weakness (periodic paralysis), changes in heart rhythm (arrhythmia), and intellectual and developmental abnormalities. Other features can include low-set ears, widely spaced eyes, small mandible, fifth-digit clinodactyly, syndactyly, short stature, and scoliosis. Speak to a genetic counselor or a medical geneticist if you have questions about Andersen-Tawil syndrome. ...
TY - JOUR. T1 - Destabilization of ATP-sensitive potassium channel activity by novel KCNJ11 mutations identified in congenital hyperinsulinism. AU - Lin, Yu Wen. AU - Bushman, Jeremy D.. AU - Yan, Fei Fei. AU - Haidar, Sara. AU - MacMullen, Courtney. AU - Ganguly, Arupa. AU - Stanley, Charles A.. AU - Shyng, Show-Ling. PY - 2008/4/4. Y1 - 2008/4/4. N2 - The inwardly rectifying potassium channel Kir6.2 is the pore-forming subunit of the ATP-sensitive potassium (KATP) channel, which controls insulin secretion by coupling glucose metabolism to membrane potential in β-cells. Loss of channel function because of mutations in Kir6.2 or its associated regulatory subunit, sulfonylurea receptor 1, causes congenital hyperinsulinism (CHI), a neonatal disease characterized by persistent insulin secretion despite severe hypoglycemia. Here, we report a novel KATP channel gating defect caused by CHI-associated Kir6.2 mutations at arginine 301 (to cysteine, glycine, histidine, or proline). These mutations in ...
Derst, C.; Wischmeyer, E.; Preisig-Mueller, R.; Spauschus, A.; Konrad, M.; Hensen, P.; Jeck, N.; Seyberth, H. W.; Daut, J.; Karschin, A.: A hyperprostaglandin E syndrome mutation in Kir1.1 (renal outer medullary potassium) channels reveals a crucial residue for channel function in Kir1.3 channels. Journal of Biological Chemistry 273, pp. 23884 - 23891 (1998 ...
Polyamine block of inwardly rectifying potassium (Kir) channels underlies their key functional property of preferential conduction of inward K+ currents (Ficker et al., 1994; Lopatin et al., 1994, 1995; Fakler et al., 1995). As a rapid and voltage-dependent process, polyamine-mediated inward rectification provides a mechanism for moment-to-moment regulation of K+ currents in excitable tissues, shaping both the action potential and resting membrane potential in tissues such as myocardium (Bianchi et al., 1996; Lopatin et al., 2000; Priori et al., 2005; Schulze-Bahr, 2005). Akin to the ongoing challenges to understanding voltage-dependent gating of the Kv channel family, development of a molecular description of steeply voltage-dependent polyamine block is an important issue for understanding the fundamental basis of strongly rectifying Kir channel activity.. Appropriate kinetic models describe polyamine block as a multistep process, incorporating sequentially linked "shallow" and "deep" binding ...
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 ...
Introduction: Andersen-Tawil syndrome (ATS) due to Kir2.1mutations typically manifests as periodic paralysis, cardiac arrhythmias and developmental abnormalities but is often difficult to diagnose clinically. This study was undertaken to determine whether sarcolemmal dysfunction could be identified with muscle velocity recovery cycles (MVRCs). Methods: Eleven genetically confirmed ATS patients and 20 normal controls were studied. MVRCs were recorded with 1, 2, and 5 conditioning stimuli and with single conditioning stimuli during intermittent repetitive stimulation at 20 Hz, in addition to the long exercise test. Results: ATS patients had longer relative refractory periods (P , 0.0001) and less early supernormality, consistent with membrane depolarization. Patients had reduced enhancement of late supernormality with 5 conditioning stimuli (P , 0.0001), and less latency reduction during repetitive stimulation (P , 0.001). Patients were separated completely from controls by combining MVRC and ...
AIMS/HYPOTHESIS: The pancreatic ATP-sensitive potassium (KATP) channel plays a pivotal role in linking beta cell metabolism to insulin secretion. Mutations in KATP channel genes can result in hypo- or hypersecretion of insulin, as in neonatal diabetes mellitus and congenital hyperinsulinism, respectively. To date, all patients affected by neonatal diabetes due to a mutation in the pore-forming subunit of the channel (Kir6.2, KCNJ11) are heterozygous for the mutation. Here, we report the first clinical case of neonatal diabetes caused by a homozygous KCNJ11 mutation. METHODS: A male patient was diagnosed with diabetes shortly after birth. At 5 months of age, genetic testing revealed he carried a homozygous KCNJ11 mutation, G324R, (Kir6.2-G324R) and he was successfully transferred to sulfonylurea therapy (0.2 mg kg(-1) day(-1)). Neither heterozygous parent was affected. Functional properties of wild-type, heterozygous and homozygous mutant KATP channels were examined after heterologous expression in
d_iris ,- dist(iris2) # method=man # is a bit better hc_iris ,- hclust(d_iris, method = complete) iris_species ,- rev(levels(iris[,5])) library(dendextend) dend ,- as.dendrogram(hc_iris) # order it the closest we can to the order of the observations: dend ,- rotate(dend, 1:150) # Color the branches based on the clusters: dend ,- color_branches(dend, k=3) #, groupLabels=iris_species) # Manually match the labels, as much as possible, to the real classification of the flowers: labels_colors(dend) ,- rainbow_hcl(3)[sort_levels_values( as.numeric(iris[,5])[order.dendrogram(dend)] )] # We shall add the flower type to the labels: labels(dend) ,- paste(as.character(iris[,5])[order.dendrogram(dend)], (,labels(dend),), sep = ) # We hang the dendrogram a bit: dend ,- hang.dendrogram(dend,hang_height=0.1) # reduce the size of the labels: # dend ,- assign_values_to_leaves_nodePar(dend, 0.5, lab.cex) dend ,- set(dend, labels_cex, 0.5) # And plot: par(mar = c(3,3,3,7)) plot(dend, main = ...
The inward rectifier K+ channels contain two putative membrane-spanning domains per subunit (M1, M2) and a pore (P) region, which is similar to the H5 domain of voltage-gated K+ channels. Here we have used Fourier transform infrared (FTIR) and CD spectroscopy to analyse the secondary structures of synthetic peptides corresponding to the M1, M2 and P regions of ROMK1 in aqueous solution, in organic solvents and in phospholipid membranes. A previous CD study was unable to provide any structural data on a similar P peptide [Ben-Efraim and Shai (1997) Biophys. J. 72, 85-96]. However, our FTIR and CD spectroscopic analyses indicate that this peptide adopts an α-helical structure when reconstituted into dimyristoyl phosphatidylcholine vesicles and lysophosphatidyl choline (LPC) micelles as well as in trifluoroethanol (TFE) solvent. This result is in good agreement with a previous study on a peptide corresponding to the pore domain of a voltage-gated K+ channel [Haris, Ramesh, Sansom, Kerr, Srai ...
Closure of ATP-regulated K(+) channels (K(ATP) channels) plays a central role in glucose-stimulated insulin secretion in beta cells. K(ATP) channels are also highly expressed in glucagon-producing alpha cells, where their function remains unresolved. Under hypoglycaemic conditions, K(ATP) channels are open in alpha cells but their activity is low and only ~1% of that in beta cells. Like beta cells, alpha cells respond to hyperglycaemia with K(ATP) channel closure, membrane depolarisation and stimulation of action potential firing. Yet, hyperglycaemia reciprocally regulates glucagon (inhibition) and insulin secretion (stimulation). Here we discuss how this conundrum can be resolved and how reduced K(ATP) channel activity, via membrane depolarisation, paradoxically reduces alpha cell Ca(2+) entry and glucagon exocytosis. Finally, we consider whether the glucagon secretory defects associated with diabetes can be attributed to impaired K(ATP) channel regulation and discuss the potential for remedial
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. KCNJ13 has a very low single channel conductance, low sensitivity to block by external barium and cesium, and no dependence of its inward rectification properties on the internal blocking particle magnesium. ...
1N9P: Structural Basis of Inward Rectification: Cytoplasmic Pore of the G Protein-Gated Inward Rectifier GIRK1 at 1.8 A Resolution
The capability of adapting cellular function and energy metabolism to varying physiological and pathological conditions is vitally important in animal cells. In the present work, we show that the Fox family may play a central role in expression of both molecular sensors of energy status and key regulatory genes of energy metabolism. First, in atrial cells, the expression of FoxO1, -O3, and -F2 cause increased expression of KATP channel subunits (the quintessential metabolic sensors7) and selective up- and downregulation of specific metabolic genes. A causal relationship between FoxO and KIR6.1 expression is demonstrated by electrophoretic mobility-shift assay and by experiments with siRNAs. Second, FoxO1, -O3, -F2, and -J2 are distributed unevenly within different cardiac chambers of the neonatal rat, in association with channel subunits KIR6.1, SUR1A, and SUR2B and 9 metabolic genes.42,43,50 Third, the periinfarcted zone of the rat left ventricle reveals an impressive plasticity of FoxO1, -O3, ...
This study is the first to demonstrate the critical role of a dystrophin isoform for the targeting and subcellular distribution of a potassium channel in glial cells. Our immunocytochemical and electrophysiological results demonstrate that functional expression of the dystrophin isoform Dp71 is necessary for the highly asymmetric expression of the inwardly rectifying potassium channel Kir4.1 in the main glial cell type in retina, the Müller cells.. Genetic inactivation of the weakly inwardly rectifying potassium channel Kir4.1 in mice demonstrated that this particular Kir subunit sets the membrane potential in Müller cells and underlies the main potassium conductance in these cells (Kofuji et al., 2000). Such marked asymmetric and clustered distribution of Kir4.1 subunits in these specialized glial cells has presumably the important physiological function of promoting the efficient buffering of extracellular potassium concentration in the retina (Newman et al., 1984). Although the cellular ...
Patients with permanent neonatal diabetes usually present within the first three months of life and need insulin treatment. In most, the cause is unknown. Because ATP-sensitive potassium (KATP) channels mediate glucose-stimulated insulin secretion from the pancreatic beta cells, activating mutations in the gene encoding the Kir6.2 subunit of this channel (KCNJ11) cause neonatal diabetes. Genotyping identifies the exact molecular etiology of early onset insulin requiring diabetes and has the potential to alter the management of the patient, who would otherwise be insulin dependent for life. Method: We identified a 6 year-old child who presented at 3 months of age with diabetic ketoacidosis. Blood samples for molecular genetic analysis were done. Results: The patient was diagnosed as a heterozygous for a missense mutation in the (KCNJ11) gene, for which she switched to sulphonylurea with a dose of 0.05 mg/kg/day. Conclusion: the need for medical practitioners to consider molecular testing for all patients
Predicted to have ATP-activated inward rectifier potassium channel activity. Predicted to be involved in potassium ion import across plasma membrane and regulation of ion transmembrane transport. Predicted to localize to plasma membrane. Used to study hypertrichotic osteochondrodysplasia Cantu type. Orthologous to human KCNJ8 (potassium inwardly rectifying channel subfamily J member 8 ...
Potassium channel openers (KCOs; e.g., P1075, pinacidil) exert their effects on excitable cells by opening ATP-sensitive potassium channels. These channels are heteromultimers composed with a 4:4 stoichiometry of an inwardly rectifying K+ channel subunit plus a regulatory subunit comprising the receptor sites for hypoglycemic sulfonylureas and KCOs (a sulfonylurea receptor). To elucidate stoichiometry of KCO action, we analyzed P1075 sensitivity of channels coassembled from sulfonylurea receptor isoforms with high or low P1075 affinity. Concentration activation curves for cDNA ratios of 1:1 or 1:10 resembled those for channel opening resulting from interaction with a single site, whereas models for activation requiring occupation of two, three, or four sites were incongruous. We conclude KCO-induced channel activation to be mediated by interaction with a single binding site per tetradimeric complex.. ...
Epilepsy, characterized by recurrent seizures, affects 1% of the general population. Interestingly, 25% of diabetics develop seizures with a yet unknown mechanism. Hyperglycemia downregulates inwardly rectifying potassium channel 4.1 (Kir4.1) in cultured astrocytes. Therefore, the present study aims to determine if downregulation of functional astrocytic Kir4.1 channels occurs in brains of type 2 diabetic mice and could influence hippocampal neuronal hyperexcitability. Using whole-cell patch clamp recording in hippocampal brain slices from male mice, we determined the electrophysiological properties of stratum radiatum astrocytes and CA1 pyramidal neurons. In diabetic mice, astrocytic Kir4.1 channels were functionally downregulated as evidenced by multiple characteristics including depolarized membrane potential, reduced barium-sensitive Kir currents and impaired potassium uptake capabilities of hippocampal astrocytes. Furthermore, CA1 pyramidal neurons from diabetic mice displayed increased spontaneous
TY - JOUR. T1 - Investigation of the subunit composition and the pharmacology of the mitochondrial ATP-dependent K+ channel in the brain. AU - Lacza, Zsombor. AU - Snipes, James A.. AU - Kis, Béla. AU - Szabó, Csaba. AU - Grover, Gary. AU - Busija, David W.. PY - 2003/12/19. Y1 - 2003/12/19. N2 - Selective activation of mitoKATP channels can protect the brain or cultured neurons against a variety of anoxic or metabolic challenges. However, little is known about the subunit composition or functional regulation of the channel itself. In the present study, we sought to characterize the mitoKATP channel in the mouse brain using overlapping approaches. First, we determined that mitochondria contain the pore-forming Kir6.1 and Kir6.2 subunits with Western blotting, immunogold electron microscopy and the identification of mitochondrial transport sequences. In contrast, we found no evidence for the presence of either known sulfonylurea receptors (SUR1 or SUR2) in the mitochondria. However, the ...
Context: ATP-sensitive potassium (KATP) stations regulate insulin secretion by coupling glucose rate of metabolism to β-cell membrane potential. gating properties of the producing channels were assessed biochemically and electrophysiologically. Results: Both E208K and V324M augment channel response to MgADP activation without altering level of sensitivity to ATP4? or sulfonylureas. Remarkably whereas E208K causes only a small increase in MgADP response consistent with the slight transient diabetes phenotype V324M causes a severe activating gating defect. Unlike E208K V324M also impairs channel expression in the cell surface which is definitely expected ON-01910 to dampen its practical impact on β-cells. When either mutation was combined with a mutation in the second nucleotide binding website of SUR1 previously shown to abolish Mg-nucleotide response the activating effect of E208K and V324M was also abolished. Moreover combination of E208K and V324M results in channels with Mg-nucleotide level ...
View mouse Kcnj16 Chr11:110968033-111027968 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
View mouse Kcnj2 Chr11:111066164-111076821 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
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, ...
G protein-coupled inwardly-rectifying potassium channel Inward-rectifier potassium ion channel GRCh38: Ensembl release 89: ... "Entrez Gene: KCNJ6 potassium inwardly-rectifying channel, subfamily J, member 6". Masotti, Andrea; Uva, Paolo; Davis-Keppen, ... Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacol Rev. 57 (4): 509-26. doi:10.1124 ... "G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase". J. Biol. ...
Potassium inwardly-rectifying channel, subfamily J, member 13 (KCNJ13) is a human gene encoding the Kir7.1 protein. Inward- ... Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacological Reviews. 57 (4): 509-26. ... KCNJ13 potassium inwardly-rectifying channel, subfamily J, member 13". Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, ... "Cloning and characterization of a novel human inwardly rectifying potassium channel predominantly expressed in small intestine ...
Isomoto S, Kondo C, Kurachi Y (February 1997). "Inwardly rectifying potassium channels: their molecular heterogeneity and ... Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacological Reviews. 57 (4): 509-26. ... Since all potassium channels share the same ion conducting outer pore structure, Lq2 binds to all three potassium channel types ... It blocks various potassium channels, among others the inward-rectifier potassium ion channel ROMK1. Lq2 is also known as ...
Nomenclature and Molecular Relationships of Inwardly Rectifying Potassium Channels". Pharmacological Reviews. 57 (4): 509-26. ... "Cloning and expression of an inwardly rectifying ATP-regulated potassium channel". Nature. 362 (6415): 31-8. doi:10.1038/ ... Nichol's research investigates the biology of ion channels, particularly potassium channels, and their role in diabetes ... Nichols, C. G.; Lopatin, A. N. (1997). "Inward Rectifier Potassium Channels". Annual Review of Physiology. 59: 171-191. doi: ...
G protein-coupled inwardly-rectifying potassium channel Inward-rectifier potassium ion channel GRCh38: Ensembl release 89: ... Potassium inwardly-rectifying channel, subfamily J, member 3, also known as KCNJ3 or Kir3.1, is a human gene. Potassium ... 1996). "A recombinant inwardly rectifying potassium channel coupled to GTP- binding proteins". J. Gen. Physiol. 107 (3): 381-97 ... Plummer HK, Dhar MS, Cekanova M, Schuller HM (2006). "Expression of G-protein inwardly rectifying potassium channels (GIRKs) in ...
"Entrez Gene: KCNJ10 potassium inwardly-rectifying channel, subfamily J, member 10". Bockenhauer D, Feather S, Stanescu HC, ... Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacological Reviews. 57 (4): 509-26. ... of the Ca2+-sensing receptor with the inwardly rectifying potassium channels Kir4.1 and Kir4.2 results in inhibition of channel ... "Assignment of the glial inwardly rectifying potassium channel KAB-2/Kir4.1 (Kcnj10) gene to the distal region of mouse ...
Rae JL, Shepard AR (1998). "Inwardly rectifying potassium channels in lens epithelium are from the IRK1 (Kir 2.1) family". Exp ... Dart C, Leyland ML (2001). "Targeting of an A kinase-anchoring protein, AKAP79, to an inwardly rectifying potassium channel, ... Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacol. Rev. 57 (4): 509-26. doi: ... Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacol. Rev. 57 (4): 509-26. doi: ...
G protein-coupled inwardly-rectifying potassium channel Inward-rectifier potassium ion channel GRCh38: Ensembl release 89: ... "Entrez Gene: KCNJ9 potassium inwardly-rectifying channel, subfamily J, member 9". Jelacic TM, Kennedy ME, Wickman K, Clapham DE ... Plummer HK, Dhar MS, Cekanova M, Schuller HM (2006). "Expression of G-protein inwardly rectifying potassium channels (GIRKs) in ... Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacological Reviews. 57 (4): 509-26. ...
Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacol. Rev. 57 (4): 509-26. doi: ... KCNJ11 potassium inwardly-rectifying channel, subfamily J, member 11". Smith AJ, Taneja TK, Mankouri J, Sivaprasadarao A (2007 ... "Mapping of the physical interaction between the intracellular domains of an inwardly rectifying potassium channel, Kir6.2". J. ... Inward-rectifier potassium ion channel Potassium channel GRCh38: Ensembl release 89: ENSG00000187486 - Ensembl, May 2017 GRCm38 ...
"Entrez Gene: potassium inwardly-rectifying channel". Foster DB, Ho AS, Rucker J, Garlid AO, Chen L, Sidor A, Garlid KD, ... The renal outer medullary potassium channel (ROMK) is an ATP-dependent potassium channel (Kir1.1) that transports potassium out ... In humans, ROMK is encoded by the KCNJ1 (potassium inwardly-rectifying channel, subfamily J, member 1) gene. Multiple ... Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacological Reviews. 57 (4): 509-26. ...
"Entrez Gene: KCNJ12 potassium inwardly-rectifying channel, subfamily J, member 12". Leonoudakis D, Conti LR, Anderson S, Radeke ... Namba N, Mori R, Tanaka H, Kondo I, Narahara K, Seino Y (1998). "The inwardly rectifying potassium channel subunit Kir2.2v ( ... Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacological Reviews. 57 (4): 509-26. ... "Regulation of cardiac inwardly rectifying potassium current IK1 and Kir2.x channels by endothelin-1". Journal of Molecular ...
Potassium inwardly-rectifying channel, subfamily J, member 4, also known as KCNJ4 or Kir2.3, is a human gene. Several different ... The latter are referred to as inwardly rectifying K+ channels, and they have a greater tendency to allow potassium to flow into ... Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacol. Rev. 57 (4): 509-26. doi: ... KCNJ4 potassium inwardly-rectifying channel, subfamily J, member 4". Leonoudakis D, Conti LR, Anderson S, Radeke CM, McGuire LM ...
Embedded in the cell membrane is also the G protein-coupled inwardly-rectifying potassium channel. When a Gβγ or Gα(GTP) ... and potassium ions are pumped out of the neuron.[45] The activation of the potassium channel and subsequent deactivation of the ... Yamada M, Inanobe A, Kurachi Y (December 1998). "G protein regulation of potassium ion channels". Pharmacological Reviews. 50 ( ... molecule binds to the C-terminus of the potassium channel, it becomes active, ...
A G protein-coupled inwardly-rectifying potassium channel, abbreviated as GIRK.. ...
"Cloning and expression of an inwardly rectifying ATP-regulated potassium channel". Nature. 362 (6415): 31-8. doi:10.1038/ ... His laboratory identified a potassium excretion regulatory channel involved in Bartter's syndrome type II, two sodium chloride ...
... including the positively influenced inwardly rectifying potassium channels (=Kir or IRK),[14] and calcium channels, which are ... IN the visual system, cannabinoids agonist induce a dose dependent modulation of calcium, chloride and potassium channels. This ... "IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the ... In summary, CB1 receptor activity has been found to be coupled to certain ion channels, in the following manner:[10] ...
... including the positively influenced inwardly rectifying potassium channels (=Kir or IRK),[14] and calcium channels, which are ... chloride and potassium channels. This alters vertical transmission between photoreceptor, bipolar and ganglion cells. Altering ... "IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the ... In summary, CB1 receptor activity has been found to be coupled to certain ion channels, in the following manner:[10] ...
Examples include coupling to and activating G protein-coupled inwardly-rectifying potassium channels. Small GTPases also bind ... G proteins regulate metabolic enzymes, ion channels, transporter proteins, and other parts of the cell machinery, controlling ...
"Kappa-opioid receptors couple to inwardly rectifying potassium channels when coexpressed by Xenopus oocytes". Molecular ... KORs also couple to inward-rectifier potassium and to N-type calcium ion channels. Recent studies have also demonstrated that ... "Opioid Receptors: κ". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. ...
It acts as an inhibitor of G protein-coupled inwardly-rectifying potassium channels (GIRKs). The drug was discovered in the ... "A Novel Antidepressant-like Action of Drugs Possessing GIRK Channel Blocking Action in Rats". Yakugaku Zasshi. 130 (5): 699-705 ... Through inhibition of GIRK channels, tipepidine increases dopamine levels in the nucleus accumbens, but without increasing ... "Tipepidine activates VTA dopamine neuron via inhibiting dopamine D₂ receptor-mediated inward rectifying K⁺ current". ...
G protein-coupled inwardly-rectifying potassium channel Inward-rectifier potassium ion channel GRCh38: Ensembl release 89: ... KCNJ5 potassium inwardly-rectifying channel, subfamily J, member 5". Online Mendelian Inheritance in Man (OMIM) potassium ... Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacological Reviews. 57 (4): 509-26. ... "A recombinant inwardly rectifying potassium channel coupled to GTP-binding proteins". The Journal of General Physiology. 107 (3 ...
Inwardly rectifying potassium channels have been shown to require docking of PIP2 for channel activity. PIP2 is regulated by ... P2 binding sites in Kir2.1 inwardly rectifying potassium channels". FEBS Letters. 490 (1-2): 49-53. doi:10.1016/S0014-5793(01) ... PIP2 regulates the function of many membrane proteins and ion channels, such as the M-channel. The products of the PLC ... One mechanism for direct effect of PtdIns(4,5)P2 is opening of Na+ channels as a minor function in growth hormone release by ...
Isomoto, S; Kondo, C; Kurachi, Y (1997). "Inwardly rectifying potassium channels: their molecular heterogeneity and function". ... The second type of potassium channel that tertiapin blocks is the calcium activated large conductance potassium channel (BK). ... inward rectifier potassium channels (Kir) and calcium activated large conductance potassium channels (BK). Tertiapin is a ... 8 nM for GIRK1/4 channels and Kd = 2 nM for ROMK1 channels. In contrast to the voltage-gated K+ channels, Kir channels are more ...
"Clustering and enhanced activity of an inwardly rectifying potassium channel, Kir4.1, by an anchoring protein, PSD-95/SAP90". ... ligand-gated ion channel activity. • potassium channel regulator activity. • cadherin binding. • Ras guanyl-nucleotide exchange ... regulation of potassium ion import. • regulation of voltage-gated potassium channel activity involved in ventricular cardiac ... ion channel binding. • cytoskeletal protein binding. • protein C-terminus binding. • ionotropic glutamate receptor binding. • ...
... inwardly rectifying, Kir (IPR016449) *Inward rectifier potassium channel 13 (IPR008062) *Potassium channel, inwardly rectifying ... Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are ... Potassium channel, inwardly rectifying, Kir (IPR016449). Short name: K_chnl_inward-rec_Kir ... Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability ...
Potassium channel, inwardly rectifying, Kir (IPR016449). *Potassium channel, inwardly rectifying, transmembrane domain ( ... Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are ... Potassium channel, inwardly rectifying, Kir, cytoplasmic (IPR013518). Short name: K_chnl_inward-rec_Kir_cyto ... Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability ...
The G protein-coupled inwardly-rectifying potassium channels (GIRKs) are a family of inward-rectifier potassium ion channels ... G protein-coupled inwardly-rectifying potassium channels are a type of G protein-gated ion channels because of this direct ... G Protein-Coupled Inwardly-Rectifying Potassium Channels at the US National Library of Medicine Medical Subject Headings (MeSH) ... "The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K+-channel proteins". Nature. 374 ( ...
In the brain inwardly rectifying potassium channel Kir7.1 subunits are predominantly expressed in the choroid plexus and ... Inwardly rectifying K+ channel Kir7.1 is highly expressed in thyroid follicular cells, intestinal epithelial cells and choroid ... Partial gene structure and assignment to chromosome 2q37 of the human inwardly rectifying K+ channel (Kir7.1) gene (KCNJ13). ... Specific localization of an inwardly rectifying K(+) channel, Kir4.1, at the apical membrane of rat gastric parietal cells; its ...
Rapid Activation of Inwardly Rectifying Potassium Channels by Immobile G-Protein-Coupled Receptors. Robert M. Lober, Miguel A. ... 2002) G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase. J ... Rapid Activation of Inwardly Rectifying Potassium Channels by Immobile G-Protein-Coupled Receptors ... Rapid Activation of Inwardly Rectifying Potassium Channels by Immobile G-Protein-Coupled Receptors ...
J:51106 Mouri T, et al., Assignment of mouse inwardly rectifying potassium channel Kcnj16 to the distal region of mouse ... inwardly rectifying, Kir. IPR008061 Potassium channel, inwardly rectifying, Kir5. IPR013518 Potassium channel, inwardly ... KCNJ16, potassium voltage-gated channel subfamily J member 16. Orthology source: HomoloGene, HGNC ...
IPR013518 Potassium channel, inwardly rectifying, Kir, cytoplasmic. IPR013673 Potassium channel, inwardly rectifying, Kir, N- ... IPR016449 Potassium channel, inwardly rectifying, Kir. IPR003271 Potassium channel, inwardly rectifying, Kir2.1 ... J:4135 Kubo Y, et al., Primary structure and functional expression of a mouse inward rectifier potassium channel [see comments ... KCNJ2, potassium voltage-gated channel subfamily J member 2. Orthology source: HomoloGene, HGNC ...
... potassium inwardly rectifying channel subfamily J member 5), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol ... inward rectifier potassium channel activity inward rectifier potassium channel activity protein binding plasma membrane ... inward rectifier potassium channel activity inward rectifier potassium channel activity protein binding plasma membrane ... inward rectifier potassium channel activity T-tubule regulation of ion transmembrane transport voltage-gated potassium channel ...
... inward rectifier potassium channel activity, potassium ion import across plasma membrane ... Potassium channel, inwardly rectifying subfamily J, member 11Imported. ,p>Information which has been imported from another ... tr,F7D6C0,F7D6C0_XENTR Potassium channel, inwardly rectifying subfamily J, member 11 OS=Xenopus tropicalis OX=8364 GN=kcnj11 PE ... inward rectifier potassium channel activity Source: GO_CentralInferred from biological aspect of ancestori*. "Phylogenetic- ...
... inwardly rectifying K+ channel , potassium channel, inwardly rectifying subfamily J member 1 , potassium inwardly-rectifying ... Potassium inwardly-rectifying channel subfamily J , kir1.1 , inwardly rectifying potassium channel ROMK-2 , potassium inwardly- ... anti-Potassium Inwardly-Rectifying Channel, Subfamily J, Member 10 Antikörper * anti-Potassium Inwardly-Rectifying Channel, ... anti-Potassium Inwardly-Rectifying Channel, Subfamily J, Member 12 Antikörper * anti-Potassium Inwardly-Rectifying Channel, ...
... a strong inwardly rectifying K+ channel of 105 pS (with 140 mm Ko+), an intermediate inwardly rectifying K+ channel of 60 pS, ... Inwardly rectifying potassium (K+) channels (Kir) in Müller cells, the dominant glial cells in the retina, are supposed to be ... Expression and Clustered Distribution of an Inwardly Rectifying Potassium Channel, KAB-2/Kir4.1, on Mammalian Retinal Müller ... 1997) Clustering and enhanced activity of an inwardly rectifying potassium channel, Kir4.1, by an anchoring protein, PSD-95/ ...
Here we have cloned the rat homologue of Kir4.2 and a new isoform of an inwardly rectifying potassium channel (Kir4.2a) from ... Cloning, expression, and localization of a rat hepatocyte inwardly rectifying potassium channel. Ceredwyn E. Hill, M. Martha ... 2000) pH dependence of the inwardly rectifying potassium channel, Kir5.1, and localization in renal tubular epithelia. J Biol ... Two transcripts resembling the Kir4.2 subclass of inwardly rectifying potassium channels were found. The longer deduced isoform ...
... channels underlies their steep voltage--dependence observed in native cells. The structural determinants of polyamine blockade ... Kurata H.T., Cheng W.W.L., Nichols C.G. (2011) Polyamine Block of Inwardly Rectifying Potassium Channels. In: Pegg A., Casero, ... Polyamine blockade of inwardly rectifying potassium (Kir) channels underlies their steep voltage--dependence observed in native ... Cheng WW, Enkvetchakul D, Nichols CG (2009) KirBac1.1: its an inward rectifying potassium channel. J Gen Physiol 133:295-305 ...
Unconventional role of the inwardly rectifying potassium channel Kir2.2 as a constitutive activator of RelA in cancer. Inkyoung ... Unconventional role of the inwardly rectifying potassium channel Kir2.2 as a constitutive activator of RelA in cancer ... Unconventional role of the inwardly rectifying potassium channel Kir2.2 as a constitutive activator of RelA in cancer ... Unconventional role of the inwardly rectifying potassium channel Kir2.2 as a constitutive activator of RelA in cancer ...
Looking for abbreviations of IRPC? It is Inwardly rectifying potassium channel. Inwardly rectifying potassium channel listed as ... Inwardly rectifying potassium channel - How is Inwardly rectifying potassium channel abbreviated? https://acronyms. ... and four subunits of inwardly rectifying potassium channel ([K.. Potassium channels in health, disease & development of channel ... redirected from Inwardly rectifying potassium channel) Acronym. Definition. IRPC. Immigration Reception and Processing Centre ( ...
Potassium Channels as Targets for Ethanol: Studies of G-Protein-Coupled Inwardly Rectifying Potassium Channel 2 (GIRK2) Null ... Potassium Channels as Targets for Ethanol: Studies of G-Protein-Coupled Inwardly Rectifying Potassium Channel 2 (GIRK2) Null ... Potassium Channels as Targets for Ethanol: Studies of G-Protein-Coupled Inwardly Rectifying Potassium Channel 2 (GIRK2) Null ... Potassium Channels as Targets for Ethanol: Studies of G-Protein-Coupled Inwardly Rectifying Potassium Channel 2 (GIRK2) Null ...
anti-Potassium Inwardly-Rectifying Channel, Subfamily J, Member 11 (KCNJ11) antibody (Alexa Fluor 488) ABIN903742 from ... anti-Potassium Inwardly-Rectifying Channel, Subfamily J, Member 11 (KCNJ11) antibody (Alexa Fluor 488) from antibodies-online. ... Itemanti-Potassium Inwardly-Rectifying Channel, Subfamily J, Member 11 (KCNJ11) antibody (Alexa Fluor 488) ...
Knockdown of Inwardly Rectifying Potassium Channel Kir2.2 Suppresses Tumorigenesis by Inducing Reactive Oxygen Species-Mediated ... Knockdown of Inwardly Rectifying Potassium Channel Kir2.2 Suppresses Tumorigenesis by Inducing Reactive Oxygen Species-Mediated ... Knockdown of Inwardly Rectifying Potassium Channel Kir2.2 Suppresses Tumorigenesis by Inducing Reactive Oxygen Species-Mediated ... Knockdown of Inwardly Rectifying Potassium Channel Kir2.2 Suppresses Tumorigenesis by Inducing Reactive Oxygen Species-Mediated ...
Potassium Inwardly-Rectifying Channel, Subfamily J, Member 11 antibody for Immunocytochemistry (ICC). ... anti-Potassium Inwardly-Rectifying Channel, Subfamily J, Member 11 Antibodies * anti-Pig (Porcine) Potassium Inwardly- ... Potassium Inwardly-Rectifying Channel, Subfamily J, Member 11 (KCNJ11) Antibodies show synonyms for this antigen * kir6.2 ... Potassium Inwardly-Rectifying Channel, Subfamily J, Member 11 (KCNJ11) Alternative Name KCNJ11 / Kir6.2 (KCNJ11 Antibody ...
... an important role for the regulation of the bee antiviral immune response by ATP-sensitive inwardly rectifying potassium (KATP ... channels. We have shown that treatment with the KATP channel agonist pinacidil increases survival of bees while decreasing ... Our results suggest that KATP channels provide a significant link between cellular metabolism and the antiviral immune response ... viral replication following infection with FHV, whereas treatment with the KATP channel antagonist tolbutamide decreases ...
Potassium Inwardly-Rectifying Channel, Subfamily J, Member 11 antibody for Western Blotting (WB). ... anti-Potassium Inwardly-Rectifying Channel, Subfamily J, Member 11 Antibodies * anti-Rat (Rattus) Potassium Inwardly-Rectifying ... Potassium Inwardly-Rectifying Channel, Subfamily J, Member 11 (KCNJ11) Antibodies show synonyms for this antigen * kir6.2 ... Recommended Potassium Inwardly-Rectifying Channel, Subfamily J, Member 11 Antibody (supplied by: Log in to see ) ...
An inwardly rectifying potassium channel (Kir) is a kind of protein complex that is widely expressed on excitable and ... This review provides insight into Kir channel regulation.. キーワード: Inwardly rectifying potassium channel, Kir, structure, ... Review on Regulation of Inwardly Rectifying Potassium Channels. Junshuai Wang Tongji Hospital of Wuhan ... An inwardly rectifying potassium channel (Kir) is a kind of protein complex that is widely expressed on excitable and ...
An inwardly rectifying potassium channel (Kir) is a kind of protein complex that is widely expressed on excitable and ... This review provides insight into Kir channel regulation.. Palavras-chave: Inwardly rectifying potassium channel, Kir, ... Review on Regulation of Inwardly Rectifying Potassium Channels. Junshuai Wang Tongji Hospital of Wuhan ... An inwardly rectifying potassium channel (Kir) is a kind of protein complex that is widely expressed on excitable and ...
Endocannabinoids Modulate N-Type Calcium Channels and G-Protein-Coupled Inwardly Rectifying Potassium Channels via CB1 ... Endocannabinoids Modulate N-Type Calcium Channels and G-Protein-Coupled Inwardly Rectifying Potassium Channels via CB1 ... Endocannabinoids Modulate N-Type Calcium Channels and G-Protein-Coupled Inwardly Rectifying Potassium Channels via CB1 ... Endocannabinoids Modulate N-Type Calcium Channels and G-Protein-Coupled Inwardly Rectifying Potassium Channels via CB1 ...
... a functional link between the β-adrenergic receptor signaling pathway and the G-protein inwardly rectifying potassium channel ( ... Stimulation of GIRK channels and β-adrenergic signaling may activate similar signaling pathways in both SCLC and breast cancer ... We wanted to determine if GIRK channels were expressed in lung cancers and if a similar link exists in lung cancer. GIRK1-4 ... We feel these may be important regulatory pathways since no expression of mRNA of the GIRK channels (1 & 2) was found in ...
  • A novel sulfonylurea receptor forms with BIR (Kir6.2) a smooth muscle type ATP-sensitive K^+ channel. (nii.ac.jp)
  • Formed through association of the Kir6.2 pore and the sulfonylurea receptor, the stress-responsive ATP-sensitive K(+) channels (K(ATP) channels), with their metabolic-sensing capability and broad tissue expression, are potential candidates for integrating the systemic adaptive response to repetitive exercise. (biomedsearch.com)
  • Here, the responses of mice lacking functional Kir6.2-containing K(ATP) channels (Kir6.2-KO) were compared with wild-type controls following a 28-day endurance swimming protocol. (biomedsearch.com)
  • Thus, Kir6.2-containing K(ATP) channel activity is required for attainment of the physiologic benefits of exercise training without injury. (biomedsearch.com)
  • Only a single population of Kir channel activity, the properties of which were identical to those of K AB -2/Kir4.1 expressed in HEK293T cells, could be recorded from endfoot to the distal portion of Müller cells. (jneurosci.org)
  • In this study, expression levels of AQP4 and Kir4.1 were for the first time examined in the brainstem and cortex, along with the functional properties of Kir channels in cultured cortical astrocytes of the SOD1G93A rat model of ALS. (ac.rs)
  • Hyperglycemia downregulates inwardly rectifying potassium channel 4.1 (Kir4.1) in cultured astrocytes. (mdpi.com)
  • Therefore, the present study aims to determine if downregulation of functional astrocytic Kir4.1 channels occurs in brains of type 2 diabetic mice and could influence hippocampal neuronal hyperexcitability. (mdpi.com)
  • Our data suggest that astrocytic dysfunction due to downregulation of Kir4.1 channels may increase seizure susceptibility by impairing astrocytic ability to maintain proper extracellular homeostasis. (mdpi.com)
  • The changes in the studied channels, notably at the upper CNS level, could underline the hampered ability of astrocytes to maintain water and potassium homeostasis, thus affecting the BBB, disturbing the neuronal microenvironment, and causing motoneuronal dysfunction and death. (ac.rs)
  • Astrocytes are connected through connexin-based gap junction channels, with brain region specificities, and those networks modulate neuronal activities, such as those involved in sleep-wake cycle, cognitive, or sensory functions. (frontiersin.org)
  • We further show that chemical factors released in the brain, including those associated with neuronal activity, cause changes in the levels of PIP 2 , thereby altering endothelial potassium channel signaling and controlling cerebral blood flow. (pnas.org)
  • Using RT-PCR analysis, we found that inward rectifier K channel 6.1 (Kir6.1) and sulfonylurea 2B (SUR2B) transcripts were predominantly expressed in rabbit femoral artery. (nii.ac.jp)
  • Potassium flux through hepatocellular basolateral membrane channels may provide the counterion for apical anion efflux. (physiology.org)
  • Electrophysiological properties of Kir channels make them well-suited candidates for coupling basolateral K + efflux with luminal secretion in cells, like hepatocytes, that do not undergo the oscillations in membrane potential that are requisite for opening of voltage-gated K + channels (Kv), and/or do not couple increases in cytosolic Ca 2+ to secretion ( 20 ). (physiology.org)
  • Enkvetchakul D, Jeliazkova I, Nichols CG (2005) Direct modulation of Kir channel gating by membrane phosphatidylinositol 4,5-bisphosphate. (springer.com)
  • Left: Activation (opening) of a K + channel (gray) in the cell membrane allows K + to flux out of the cell, causing a decrease in E m (ie, hyperpolarization) and consequent inhibition (closure) of voltage-activated Ca 2+ channels (white) and a decrease in cytosolic Ca 2+ levels, resulting in vascular muscle relaxation (vasodilatation). (ahajournals.org)
  • However, when the membrane potential is set positive to the channel's resting potential (e.g. +60 mV), these channels pass very little current. (wikipedia.org)
  • They, along with the "leak" channels, establish the resting membrane potential of the cell. (wikipedia.org)
  • Healthy cerebrovascular myocytes express members of several different ion channel families which regulate resting membrane potential, vascular diameter, and vascular tone and are involved in cerebral autoregulation. (hindawi.com)
  • Inward rectifiers play a role in setting cellular membrane potentials, and closing of these channels upon depolarization permits the occurrence of long duration action potentials with a plateau phase. (wikipedia.org)
  • In pancreatic β-cells, ATP-sensitive potassium (K ATP ) channels control insulin secretion by coupling metabolism to membrane electrical activity. (diabetesjournals.org)
  • ATP applied to the intracellular face of the membrane inhibited KATP channel activity with a Ki of 17 microM, an effect that could be counteracted by Mg-ADP and Mg-GDP. (nih.gov)
  • Ion channels establish and regulate membrane potentials in excitable and non-excitable cells. (biologists.org)
  • Knowledge of how membrane conduction properties changed during the evolution of multicellularity would be aided by the comparative analysis of K + channels from phyla occupying basal positions. (biologists.org)
  • Inwardly rectifying potassium channels, such as Kir2.6, maintain resting membrane potential in excitable cells and aid in repolarization of cells following depolarization. (wikipedia.org)
  • The IRK2 channels showed strong inward rectification in the cell-attached configuration of the patch-clamp method. (nii.ac.jp)
  • polyamine to the channel and (2) raise a possibility that artificial polyvalent cations introduced into cardiocytes might be utilized to pharmacologically modulate the strong inward rectification of the channels induced by intracellular polyamines. (nii.ac.jp)