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.
Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.
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.
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.
An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.
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.
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.
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.
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.
10-carbon saturated monocarboxylic acids.
Organic compounds containing both the hydroxyl and carboxyl radicals.
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.
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.
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)
A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.
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)
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.
A class of drugs that act by selective inhibition of calcium influx through cellular membranes.
A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)
Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.
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.
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.
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.
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.
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).
Potassium channels whose activation is dependent on intracellular calcium concentrations.
The excitable plasma membrane of a muscle cell. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
Exposure of myocardial tissue to brief, repeated periods of vascular occlusion in order to render the myocardium resistant to the deleterious effects of ISCHEMIA or REPERFUSION. The period of pre-exposure and the number of times the tissue is exposed to ischemia and reperfusion vary, the average being 3 to 5 minutes.
Compounds with a core of fused benzo-pyran rings.
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.
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.
CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.
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).
The ability of a substrate to allow the passage of ELECTRONS.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Drugs used to cause dilation of the blood vessels.
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.
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.
A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.
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.
A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.
A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.
Substances which lower blood glucose levels.
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.
Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.
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.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
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.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
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.
A familial, nontransient HYPOGLYCEMIA with defects in negative feedback of GLUCOSE-regulated INSULIN release. Clinical phenotypes include HYPOGLYCEMIA; HYPERINSULINEMIA; SEIZURES; COMA; and often large BIRTH WEIGHT. Several sub-types exist with the most common, type 1, associated with mutations on an ATP-BINDING CASSETTE TRANSPORTERS (subfamily C, member 8).
Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.
The rate dynamics in chemical or physical systems.
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.
The mitochondria of the myocardium.
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.
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.
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.
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.
A voltage-gated potassium channel that is expressed primarily in the HEART.
Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.
Established cell cultures that have the potential to propagate indefinitely.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
An oral sulfonylurea hypoglycemic agent which stimulates insulin secretion.
A tricyclo bridged hydrocarbon.
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.
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.
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.
A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.
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.
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.
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.
Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.
A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.
Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).
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)
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.
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.
A barbiturate that is administered intravenously for the production of complete anesthesia of short duration, for the induction of general anesthesia, or for inducing a hypnotic state. (From Martindale, The Extra Pharmacopoeia, 30th ed, p919)
The nonstriated involuntary muscle tissue of blood vessels.
The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.
A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.
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.
An edible species of the family Ranidae, occurring in Europe and used extensively in biomedical research. Commonly referred to as "edible frog".
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.
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.
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.
A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.
The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.
The hollow, muscular organ that maintains the circulation of the blood.
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.
CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.
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).)
Azoles of one NITROGEN and two double bonds that have aromatic chemical properties.
A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra).
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.
A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.
A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).
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.
Compounds containing the PhCH= radical.
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.
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.
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)
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.
Elements of limited time intervals, contributing to particular results or situations.
The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.
A benign tumor of the PANCREATIC BETA CELLS. Insulinoma secretes excess INSULIN resulting in HYPOGLYCEMIA.
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.
Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.
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.
CALCIUM CHANNELS located in the neurons of the brain.
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.
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.
Damage to the MYOCARDIUM resulting from MYOCARDIAL REPERFUSION (restoration of blood flow to ischemic areas of the HEART.) Reperfusion takes place when there is spontaneous thrombolysis, THROMBOLYTIC THERAPY, collateral flow from other coronary vascular beds, or reversal of vasospasm.
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.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
Carrier of aroma of butter, vinegar, coffee, and other foods.
CALCIUM CHANNELS located in the neurons of the brain. They are inhibited by the marine snail toxin, omega conotoxin MVIIC.
A technique in which tissue is rendered resistant to the deleterious effects of prolonged ISCHEMIA and REPERFUSION by prior exposure to brief, repeated periods of vascular occlusion. (Am J Physiol 1995 May;268(5 Pt 2):H2063-7, Abstract)
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A toxic dye, chemically related to trinitrophenol (picric acid), used in biochemical studies of oxidative processes where it uncouples oxidative phosphorylation. It is also used as a metabolic stimulant. (Stedman, 26th ed)
A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.
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.
A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
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.
The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
Use of electric potential or currents to elicit biological responses.
Gases or volatile liquids that vary in the rate at which they induce anesthesia; potency; the degree of circulation, respiratory, or neuromuscular depression they produce; and analgesic effects. Inhalation anesthetics have advantages over intravenous agents in that the depth of anesthesia can be changed rapidly by altering the inhaled concentration. Because of their rapid elimination, any postoperative respiratory depression is of relatively short duration. (From AMA Drug Evaluations Annual, 1994, p173)
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A highly poisonous compound that is an inhibitor of many metabolic processes and is used as a test reagent for the function of chemoreceptors. It is also used in many industrial processes.
A 20-carbon-chain fatty acid, unsaturated at positions 8, 11, and 14. It differs from arachidonic acid, 5,8,11,14-eicosatetraenoic acid, only at position 5.
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)
Unstable isotopes of rubidium that decay or disintegrate emitting radiation. Rb atoms with atomic weights 79-84, and 86-95 are radioactive rubidium isotopes.
A cytochrome oxidase inhibitor which is a nitridizing agent and an inhibitor of terminal oxidation. (From Merck Index, 12th ed)
Proteins prepared by recombinant DNA technology.
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.
A family of voltage-gated eukaryotic porins that form aqueous channels. They play an essential role in mitochondrial CELL MEMBRANE PERMEABILITY, are often regulated by BCL-2 PROTO-ONCOGENE PROTEINS, and have been implicated in APOPTOSIS.
Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)
Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.
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)
Relatively complete absence of oxygen in one or more tissues.
A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.
Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.
Compounds of four rings containing a nitrogen. They are biosynthesized from reticuline via rearrangement of scoulerine. They are similar to BENZYLISOQUINOLINES. Members include chelerythrine and sanguinarine.
A stable, non-explosive inhalation anesthetic, relatively free from significant side effects.
A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of SKELETAL MYOCYTES. Defects in the SCN4A gene, which codes for the alpha subunit of this sodium channel, are associated with several MYOTONIC DISORDERS.
A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.
Refers to animals in the period of time just after birth.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
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.
A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.
A flammable, poisonous gas with a characteristic odor of rotten eggs. It is used in the manufacture of chemicals, in metallurgy, and as an analytical reagent. (From Merck Index, 11th ed)
Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.
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.
The circulation of blood through the CORONARY VESSELS of the HEART.
The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.
The calcium salt of gluconic acid. The compound has a variety of uses, including its use as a calcium replenisher in hypocalcemic states.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
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.
A family of mechanosensitive sodium channels found primarily in NEMATODES where they play a role in CELLULAR MECHANOTRANSDUCTION. Degenerin sodium channels are structurally-related to EPITHELIAL SODIUM CHANNELS and are named after the fact that loss of their activity results in cellular degeneration.
The innermost layer of the three meninges covering the brain and spinal cord. It is the fine vascular membrane that lies under the ARACHNOID and the DURA MATER.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
A class of drugs that stimulate sodium influx through cell membrane channels.
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.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A condition of decreased oxygen content at the cellular level.
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.
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.
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.
The veins and arteries of the HEART.
A neurotoxic peptide, which is a cleavage product (VIa) of the omega-Conotoxin precursor protein contained in venom from the marine snail, CONUS geographus. It is an antagonist of CALCIUM CHANNELS, N-TYPE.
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.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
Arteries which arise from the abdominal aorta and distribute to most of the intestines.
The physical characteristics and processes of biological systems.
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).
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.
A neuronal cell membrane protein that combines with SNAP-25 and SYNAPTOBREVIN 2 to form a SNARE complex that leads to EXOCYTOSIS.
Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE).
The regulatory subunits of large-conductance calcium-activated potassium channels.

Two regions of sulfonylurea receptor specify the spontaneous bursting and ATP inhibition of KATP channel isoforms. (1/595)

KATP channels are heteromultimers of KIR6.2 and a sulfonylurea receptor, SUR, an ATP binding cassette (ABC) protein with several isoforms. KIR6.2 forms a channel pore whose spontaneous activity and ATP sensitivity are modulated by the receptor via an unknown interaction(s). Side by side comparison of single-channel kinetics and steady-state ATP inhibition of human beta-cell, SUR1/KIR6.2, versus cardiac, SUR2A/KIR6.2 channels demonstrate that the latter have a greater mean burst duration and open probability in the absence of nucleotides and approximately 4-fold higher IC50(ATP). We have used matched chimeras of SUR1 and SUR2A to show that the kinetics, which determine the maximal open probability (Pomax), and the ATP sensitivity are functionally separable and to identify the two segments of SUR responsible for these isoform differences. A region within the first five transmembrane domains specifies the interburst kinetics, whereas a C-terminal segment determines the sensitivity to inhibitory ATP. The separable effects of SUR on ATP inhibition and channel kinetics implies that the cytoplasmic C terminus of SUR either directly modulates the affinity of a weak ATP binding site on the inward rectifier or affects linkage between the binding site and the gate. This is the first identification of parts of an ABC protein that interact with an ion channel subunit to modulate the spontaneous activity and ATP sensitivity of the heteromeric channel.  (+info)

ATP-Sensitive K+ channel modulator binding to sulfonylurea receptors SUR2A and SUR2B: opposite effects of MgADP. (2/595)

KATP channels are heteromeric complexes of inwardly rectifying K+ channel subunits and sulfonylurea receptors (SURs). SUR2A and SUR2B, which differ within the carboxyl terminal exon 38, are characteristic for the cardiac and smooth muscle type channels, respectively. Here we compare binding of the tritiated KATP channel opener, [3H]P1075, to membranes from human embryonic kidney (HEK) cells transfected with murine SUR2A and 2B at 37 degrees C. Binding to both SURs required addition of Mg2+ and ATP in the low micromolar range. In the presence of MgATP, micromolar concentrations of MgADP, formed by the ATPase activity of the membrane preparation, increased binding to SUR2A but inhibited binding to SUR2B. Decreasing temperatures strongly reduced [3H]P1075 binding to SUR2A, whereas binding to SUR2B was increased in a bell-shaped manner. Kinetic experiments revealed a faster dissociation of the [3H]P1075-SUR2A complex, whereas the association rate constants for [3H]P1075 binding to SUR2A and 2B were similar. Openers inhibited [3H]P1075 binding to SUR2A with potencies approximately 4 times lower than to SUR2B; in contrast, glibenclamide inhibited [3H]P1075 binding to SUR2A approximately 8 times more potently than to SUR2B. The data suggest that SUR2A and 2B represent the opener receptors of cardiac and vascular smooth muscle KATP channels, respectively, and show that MgADP is an important modulator of opener binding to SUR. The different carboxyl termini of SUR2A and 2B lead to differences in the MgADP dependence and the thermodynamics of [3H]P1075 binding, as well as in the affinities for openers and glibenclamide, underlining the importance of this part of the molecule for KATP channel modulator binding.  (+info)

Sulfonylurea and K(+)-channel opener sensitivity of K(ATP) channels. Functional coupling of Kir6.2 and SUR1 subunits. (3/595)

The sensitivity of K(ATP) channels to high-affinity block by sulfonylureas and to stimulation by K(+) channel openers and MgADP (PCOs) is conferred by the regulatory sulfonylurea receptor (SUR) subunit, whereas ATP inhibits the channel through interaction with the inward rectifier (Kir6.2) subunit. Phosphatidylinositol 4, 5-bisphosphate (PIP(2)) profoundly antagonized ATP inhibition of K(ATP) channels expressed from cloned Kir6.2+SUR1 subunits, but also abolished high affinity tolbutamide sensitivity. By stabilizing the open state of the channel, PIP(2) drives the channel away from closed state(s) that are preferentially affected by high affinity tolbutamide binding, thereby producing an apparent loss of high affinity tolbutamide inhibition. Mutant K(ATP) channels (Kir6. 2[DeltaN30] or Kir6.2[L164A], coexpressed with SUR1) also displayed an "uncoupled" phenotype with no high affinity tolbutamide block and with intrinsically higher open state stability. Conversely, Kir6. 2[R176A]+SUR1 channels, which have an intrinsically lower open state stability, displayed a greater high affinity fraction of tolbutamide block. In addition to antagonizing high-affinity block by tolbutamide, PIP(2) also altered the stimulatory action of the PCOs, diazoxide and MgADP. With time after PIP(2) application, PCO stimulation first increased, and then subsequently decreased, probably reflecting a common pathway for activation of the channel by stimulatory PCOs and PIP(2). The net effect of increasing open state stability, either by PIP(2) or mutagenesis, is an apparent "uncoupling" of the Kir6.2 subunit from the regulatory input of SUR1, an action that can be partially reversed by screening negative charges on the membrane with poly-L-lysine.  (+info)

Phosphoinositides decrease ATP sensitivity of the cardiac ATP-sensitive K(+) channel. A molecular probe for the mechanism of ATP-sensitive inhibition. (4/595)

Anionic phospholipids modulate the activity of inwardly rectifying potassium channels (Fan, Z., and J.C. Makielski. 1997. J. Biol. Chem. 272:5388-5395). The effect of phosphoinositides on adenosine triphosphate (ATP) inhibition of ATP-sensitive potassium channel (K(ATP)) currents was investigated using the inside-out patch clamp technique in cardiac myocytes and in COS-1 cells in which the cardiac isoform of the sulfonylurea receptor, SUR2, was coexpressed with the inwardly rectifying channel Kir6.2. Phosphoinositides (1 mg/ml) increased the open probability of K(ATP) in low [ATP] (1 microM) within 30 s. Phosphoinositides desensitized ATP inhibition with a longer onset period (>3 min), activating channels inhibited by ATP (1 mM). Phosphoinositides treatment for 10 min shifted the half-inhibitory [ATP] (K(i)) from 35 microM to 16 mM. At the single-channel level, increased [ATP] caused a shorter mean open time and a longer mean closed time. Phosphoinositides prolonged the mean open time, shortened the mean closed time, and weakened the [ATP] dependence of these parameters resulting in a higher open probability at any given [ATP]. The apparent rate constants for ATP binding were estimated to be 0.8 and 0.02 mM(-1) ms(-1) before and after 5-min treatment with phosphoinositides, which corresponds to a K(i) of 35 microM and 5.8 mM, respectively. Phosphoinositides failed to desensitize adenosine inhibition of K(ATP). In the presence of SUR2, phosphoinositides attenuated MgATP antagonism of ATP inhibition. Kir6.2DeltaC35, a truncated Kir6.2 that functions without SUR2, also exhibited phosphoinositide desensitization of ATP inhibition. These data suggest that (a) phosphoinositides strongly compete with ATP at a binding site residing on Kir6.2; (b) electrostatic interaction is a characteristic property of this competition; and (c) in conjunction with SUR2, phosphoinositides render additional, complex effects on ATP inhibition. We propose a model of the ATP binding site involving positively charged residues on the COOH-terminus of Kir6.2, with which phosphoinositides interact to desensitize ATP inhibition.  (+info)

Role of ATP-dependent K(+) channels in the electrical excitability of early embryonic stem cell-derived cardiomyocytes. (5/595)

Single, murine embryonic stem cell-derived early stage cardiomyocytes dissociated from embryoid bodies expressed two inward rectifier K(+) channels, I(K1) and the ATP dependent K(+) current. I(K1) exhibited low density in early stage cardiomyocytes, but increased significantly in late stage cells. In contrast, the ATP dependent K(+) current was expressed at similar densities in early and late stage cardiomyocytes. This current was found to be involved in the determination of the membrane potential, since glibenclamide depolarized early cardiomyocytes and exerted a positive chronotropic effect. Some cardiomyocytes displayed a bursting behavior of action potentials, characterized by alternating periods with and without action potentials. During the phases without action potentials, the membrane potential was hyperpolarized, indicating the involvement of K(+) channels in the generation of this bursting behavior. Extracellular recording techniques were applied to spontaneously contracting areas of whole embryoid bodies. In 20% of these bursting behavior similar to that seen in the single cells was observed. In regularly beating embryoid bodies, bursting could be induced by reduction of substrates from the extracellular medium as well as by superfusion with the positive chronotropic agents Bay K 8644 or isoproterenol. Perfusion with substrate-reduced medium induced bursting behavior after a short latency, isoproterenol and Bay K 8644 resulted in a positive chronotropic response followed by bursting behavior with longer latencies. The spontaneous bursting was blocked by glibenclamide. These experimental results suggest that intermittent activation of ATP dependent K(+) channels underlies the bursting behavior observed in single cardiomyocytes and in the whole embryoid body. Conditions of metabolic stress lead to the rhythmic suppression of action potential generation. Our data indicate that ATP dependent K(+) channels play a prominent role in the cellular excitability of early cardiomyocytes.  (+info)

KATP channels and 'border zone' arrhythmias: role of the repolarization dispersion between normal and ischaemic ventricular regions. (6/595)

1. In order to investigate the role of KATP channel activation and repolarization dispersion on the 'border zone' arrhythmias induced by ischaemia-reperfusion, the effects of glibenclamide and bimakalim, agents modifying action potential (AP) duration, were studied in an in vitro model of myocardial 'border zone'. 2. The electrophysiological effects of 10 microM glibenclamide and 1 microM bimakalim (n=8 each), respectively KATP channel blocker and activator, were investigated on guinea-pig ventricular strips submitted partly to normal conditions (normal zone, NZ) and partly to simulated ischaemic then reperfused conditions (altered zone, AZ). 3. By preventing the ischaemia-induced AP shortening (P<0.0001), glibenclamide reduced the dispersion of AP duration 90% (APD90) between NZ and AZ (P<0.0001), and concomitantly inhibited the 'border zone' arrhythmias induced by an extrastimulus (ES), their absence being significantly related to the lessened APD90 dispersion (chi2=8.28, P<0.01). 4. Bimakalim, which also reduced the APD90 dispersion (P<0.005) due to differential AP shortening in normal and ischaemic tissues, decreased the incidence of myocardial conduction blocks (25% of preparations versus 83% in control, n=12, P<0.05) and favoured 'border zone' spontaneous arrhythmias (75% of preparations versus 25% in control, P<0.05). 5. During reperfusion, unlike bimakalim, glibenclamide inhibited the ES-induced arrhythmias and reduced the incidence of the spontaneous ones (12% of preparations versus 92% in control, P<0.05), this latter effect being significantly related (chi2=6.13, P<0.02) to the lessened ischaemia-induced AP shortening in the presence of glibenclamide (P<0.0001). 6. These results suggest that KATP blockade may protect the ischaemic-reperfused myocardium from 'border zone' arrhythmias concomitantly with a reduction of APD90 dispersion between normal and ischaemic regions. Conversely, KATP channel activation may modify the incidence of conduction blocks and exacerbate the ischaemia-induced 'border zone' arrhythmias.  (+info)

Activation of Ca(2+)-dependent K(+) channels contributes to rhythmic firing of action potentials in mouse pancreatic beta cells. (7/595)

We have applied the perforated patch whole-cell technique to beta cells within intact pancreatic islets to identify the current underlying the glucose-induced rhythmic firing of action potentials. Trains of depolarizations (to simulate glucose-induced electrical activity) resulted in the gradual (time constant: 2.3 s) development of a small (<0.8 nS) K(+) conductance. The current was dependent on Ca(2+) influx but unaffected by apamin and charybdotoxin, two blockers of Ca(2+)-activated K(+) channels, and was insensitive to tolbutamide (a blocker of ATP-regulated K(+) channels) but partially (>60%) blocked by high (10-20 mM) concentrations of tetraethylammonium. Upon cessation of electrical stimulation, the current deactivated exponentially with a time constant of 6.5 s. This is similar to the interval between two successive bursts of action potentials. We propose that this Ca(2+)-activated K(+) current plays an important role in the generation of oscillatory electrical activity in the beta cell.  (+info)

(+)-[3H]isradipine and [3H]glyburide bindings to heart and lung membranes from rats with monocrotaline-induced pulmonary hypertension. (8/595)

We examined the binding of a 1,4-dihydropyridine-sensitive Ca2+ channel ligand, (+)-[3H]isradipine (PN200-110), and that of an ATP-sensitive K+ (K(ATP)) channel ligand, [3H]glyburide, to heart, lung and brain membranes isolated from Sprague-Dawley rats made pulmonary hypertensive by monocrotaline, a pyrrolizidine alkaloid. A single subcutaneous injection of monocrotaline increased right ventricular systolic pressure, a measure of pulmonary arterial pressure, and the thickness of the right ventricular free wall in 3 to 4 weeks. The (+)-[3H]PN200-110 and [3H]glyburide binding site densities (Bmax) were reduced in hypertrophied right ventricles when normalized per unit protein in comparison with those of age-matched control (sham) rats, whereas the values of the dissociation constant (Kd) of both ligands bound to the hypertrophied right ventricle were not significantly changed. The [3H]PN200-110 binding to the lung membranes of the monocrotaline-induced pulmonary hypertensive rats was increased. The results indicate that the change in the binding of 1,4-dihydropyridine Ca2+ and K(ATP) channel ligands to heart membranes may contribute to the pathological alteration of cardiopulmonary structure and functions in rats with pulmonary hypertension induced by monocrotaline.  (+info)

Sarcolemmal ATP-sensitive potassium channels (KATP) act as metabolic sensors that facilitate adaptation of the left ventricle to changes in energy requirements. This study examined the mechanism by which KATP dysfunction impairs the left ventricular response to stress using transgenic mouse strains with cardiac-specific disruption of KATP activity (SUR1-tg mice) or Kir6.2 gene deficiency (Kir6.2 KO). Both SUR1-tg and Kir6.2 KO mice had normal left ventricular mass and function under unstressed conditions. Following chronic transverse aortic constriction, both SUR1-tg and Kir6.2 KO mice developed more severe left ventricular hypertrophy and dysfunction as compared with their corresponding WT controls. Both SUR1-tg and Kir6.2 KO mice had significantly decreased expression of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and a group of energy metabolism related genes at both protein and mRNA levels. Furthermore, disruption of KATP repressed expression and promoter activity of ...
Sulfonylureas are widely used to stimulate insulin secretion in type 2 diabetic patients because they close adenosine triphosphate-sensitive potassium (K(ATP)) channels in the pancreatic beta-cell membrane. This action is mediated by binding of the drug to the sulfonylurea receptor (SUR1) subunit of the channel. K(ATP) channels are also present in a range of extrapancreatic tissues, but many of these contain an alternative type of SUR subunit (SUR2A in heart and SUR2B in smooth muscle). The sulfonylurea-sensitivity of K(ATP) channels containing the different types of SUR is variable: gliclazide and tolbutamide block the beta cell, but not the cardiac or smooth muscle types of K(ATP) channels with high affinity. Glibenclamide and glimepiride, on the other hand, block channels containing SUR1 and SUR2 with similar affinity. The reversibility of the different sulfonylureas also varies. Tolbutamide and gliclazide produce a reversible inhibition of Kir6.2/SUR1 and Kir6.2/SUR2 channels, whereas glibenclamide
The family of potassium channel openers regroups drugs that share the property of activating adenosine triphosphate-sensitive potassium (K(ATP)) channels, metabolic sensors responsible for adjusting membrane potential-dependent functions to match cellular energetic demands. K(ATP) channels, widely r …
The effects of the cellular environment on innate immunity remain poorly characterized. Here, we show that in Drosophila ATP-sensitive potassium channels (K(ATP)) mediate resistance to a cardiotropic RNA virus, Flock House virus (FHV). FHV viral load in the heart rapidly increases in K(ATP) mutant flies, leading to increased viremia and accelerated death. The effect of K(ATP) channels is dependent on the RNA interference genes Dcr-2, AGO2, and r2d2, indicating that an activity associated with this potassium channel participates in this antiviral pathway in Drosophila. Flies treated with the K(ATP) agonist drug pinacidil are protected against FHV infection, thus demonstrating the importance of this regulation of innate immunity by the cellular environment in the heart. In mice, the Coxsackievirus B3 replicates to higher titers in the hearts of mayday mutant animals, which are deficient in the Kir6.1 subunit of K(ATP) channels, than in controls. Together, our data suggest that K(ATP) channel ...
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
The ATP-sensitive potassium channel (K-ATP channel) plays a key role in insulin secretion from pancreatic beta-cells. It is closed by glucose metabolism, which stimulates secretion, and opened by the drug diazoxide, which inhibits insulin release. Metabolic regulation is mediated by changes in ATP and MgADP concentration, which inhibit and potentiate channel activity, respectively. The beta-cell K-ATP channel consists of a pore-forming subunit, Kir6.2, and a regulatory subunit, SUR1. The site at which ATP mediates channel inhibition lies on Kir6.2, while the potentiatory action of MgADP involves the nucleotide-binding domains of SUR1. K-ATP channels are also activated by MgGTP and MgGDP. Furthermore, both nucleotides support the stimulatory actions of diazoxide. It is not known, however, whether guanine nucleotides mediate their effects by direct interaction with one or more of the K-ATP channel subunits or indirectly via a GTP-binding protein. We used a truncated form of Kir6.2, which expresses
The ATP-dependent potassium channels (KATP channels) were originally identified in isolated membrane patches prepared from guinea pig ventricular myocytes by Noma1 in 1983. Since their discovery in cardiac cells, KATP channels have also been discovered in many other tissues, such as smooth muscle, skeletal muscle, pancreas, and brain, in which they have been shown to couple cellular metabolism to membrane electrical activity.2 Primarily on the basis of studies using pharmacological tools, openers of KATP channels have been shown to elicit cardioprotective effects, whereas KATP channel antagonists have been shown to block the cardioprotective effects of KATP channel openers and the powerful protective effect produced by single or multiple brief episodes of ischemia to reduce myocardial infarct size, a phenomenon called ischemic preconditioning.3 Because the results of these previous studies were obtained indirectly by the use of pharmacological agonists and antagonists, the results of the present ...
Pulmonary arterial rings were vertically mounted between two stainless steel hooks in organ baths filled with 25 ml Krebs-Ringer bicarbonate solution (37°C) gassed with 95% O2and 5% CO2. One of the hooks was anchored and the other was connected to a strain gauge to measure isometric force. The rings were stretched at 10-min intervals in increments of 0.5 g to achieve optimal resting tension. Optimal resting tension was defined as the minimum amount of stretch required to achieve the largest contractile response to 40 mm KCl and was determined in preliminary experiments to be 5 g for the size of the arteries used in these experiments. After the arterial rings had been stretched to their optimal resting tension, the contractile response to 60 mm KCl was measured. After washing out KCl from the organ bath and the return of isometric tension to prestimulation values, a cumulative concentration-response curve to phenylephrine was performed in each ring. This was achieved by increasing the ...
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, ...
Expression of KATP channel subunits in hearts of mice on control and nicotinamide-rich diet. Representative progress curves for the real-time PCR amplification
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KATP channels play a key role in the regulation of insulin secretion and in the modulation of vascular tone (5,8). In the resting pancreatic β-cells, KATP channels are normally open, but when plasma glucose rises, the enhanced glucose metabolism brings about their closure. The decrease of potassium permeability leads to an increase of cytosolic calcium that triggers the release of insulin. On the other hand, KATP channels in the vascular smooth muscle cells are normally closed or inactive. When ischemia occurs, the decline in the intracellular concentration of ATP activates these channels. The subsequent hyperpolarization of the cells decreases the inward flow of calcium, resulting in vasodilation that, in turn, combats the effects of hypoxia (8).. Sulfonylureas, as a class, interact specifically with KATP channels of cell membranes. Evidence shows that though glibenclamide and other sulfonylureas promote insulin secretion by the blockade of pancreatic KATP channels, they also neutralize the ...
The sections in this article are: 1 CellularArchitecture of Pancreatic Islets2 General Aspects of Nutrient Sensing3 The Glucose‐Sensing System: A Basic Model4 Adenine Nucleotides and the Adenosine Triphosphate-Sensitive Potassium Channel5 Regulation of Glucose Metabolism in Islet β Cells6 Molecular Manipulations of Glucose‐Phosphorylating Activity in Islet Cells7 Similarities and Differences in the Metabolic Environment of β Cells and Hepatocytes8 Role of Lipids in Regulation of Insulin Secretion9 Fundamentals of Amino Acid‐Stimulated Insulin Release10 Mitochondria as Metabolic Signal Generators of Fuel‐Stimulated β Cells11 Outlook
We next measured the concentration-inhibition curve for metabolic inhibition of wild-type and mutant KATP channels, again using the perforated-patch configuration to preserve β-cell metabolism. Because the INS-1 Flp-In T-REx clone 1-1.2 retains only a poor insulin secretory response to glucose but remains responsive to methyl succinate (27), we used the latter as a metabolic substrate. Unlike some other mitochondrial substrates (28), methyl succinate (20 mmol/l) did not affect KATP channel activity either when applied directly to the inside of an excised inside-out patch (Fig. 3A) or when added to the external solution in standard whole-cell recordings (Fig. 3B). Thus, we deduce that any effect of methyl succinate on perforated-patch whole-cell KATP currents must be a consequence of substrate metabolism.. In the absence of substrate, KATP conductances were significantly smaller for WT cells than for either R201H or tetR201H cells (Fig. 3C), as expected, because they are more ATP sensitive. The ...
摘 要:硫化氢(H2S)是具有生物学效应的气体小分子,它在免疫系统中亦发挥着重要的调节功能。H2S可通过影响IL-2(Interleukin-2)的合成抑制淋巴细胞增殖;可通过激活ERK激酶(extracellular regulated protein kinases)或者KATP通道(ATP-sensitive potassium channel),促进单核巨噬细胞及中性粒细胞分泌促炎因子,导致组织损伤,诱导诸如溃疡性结肠炎、胃炎、急性胰腺炎、急性肺损伤及毒血症等多种炎症性疾病。相反,H2S还可诱导多种抑炎因子,发挥抑制炎症的作用。鉴于H2S在免疫与炎症中发挥的生理和病理效应,该文对H2S在炎症与免疫调节中的研究进展进行综述 ...
Dive into the research topics of Scavenging of 14-3-3 proteins reveals their involvement in the cell-surface transport of ATP-sensitive K,sup,+,/sup, channels. Together they form a unique fingerprint. ...
TY - JOUR. T1 - K(ATP) channels regulate mitogenically induced proliferation in primary rat hepatocytes and human liver cell lines. T2 - Implications for liver growth control and potential therapeutic targeting. AU - Malhi, Harmeet. AU - Irani, Adil N.. AU - Rajvanshi, Pankaj. AU - Suadicani, Sylvia O.. AU - Spray, David C.. AU - McDonald, Thomas V.. AU - Gupta, Sanjeev. N1 - Copyright: Copyright 2007 Elsevier B.V., All rights reserved.. PY - 2000/8/25. Y1 - 2000/8/25. N2 - To determine whether K(ATP) channels control liver growth, we used primary rat hepatocytes and several human cancer cell lines for assays. K(ATP) channel openers (minoxidil, cromakalim, and pinacidil) increased cellular DNA synthesis, whereas K(ATP) channel blockers (quinidine and glibenclamide) attenuated DNA synthesis. The channel inhibitor glibenclamide decreased the clonogenicity of HepG2 cells without inducing cytotoxicity or apoptosis. To demonstrate the specificity of drugs for K+ channels, whole-cell patch-clamp ...
TY - JOUR. T1 - Intrahippocampal infusions of K-ATP channel modulators influence spontaneous alternation performance. T2 - Relationships to acetylcholine release in the hippocampus. AU - Stefani, Mark R.. AU - Gold, Paul E.. PY - 2001/1/15. Y1 - 2001/1/15. N2 - One mechanism by which administration of glucose enhances cognitive functions may be by modulating central ATP-sensitive potassium (K-ATP) channels. K-ATP channels appear to couple glucose metabolism and neuronal excitability, with channel blockade increasing the likelihood of neurosecretion. The present experiment examined the effects of glucose and the direct K-ATP channel modulators glibenclamide and lemakalim on spontaneous alternation performance and hippocampal ACh release. Rats received either artificial CSF vehicle or vehicle plus drug for two consecutive 12 min periods via microdialysis probes (3 mm; flow rate of 2.1 μl/min) implanted in the left hippocampus. During the second 12 min period, rats were tested for spontaneous ...
Iptakalim was unable to open pancreatic β-cell KATP channels, perhaps due to the presence of the SUR1, instead of the SUR2, subunit in these cells. Moreover, an intriguing finding was that iptakalim closed pancreatic β-cell-type KATP channels. It has been reported that PNU-99963, a nonsulfonylurea-based KATP channel inhibitor that has a structure similar to the KATP channel opener pinacidil, inhibits β-cell KATP channels (Cui et al., 2003). Structurally, iptakalim is also similar to the core portion of pinacidil; therefore, it is possible that KATP channel opener analogs with such a structure can inhibit KATP channels. Iptakalim may directly block β-cell KATP channels by acting on the Kir6.2 subunit (or some closely associated regulatory proteins). It is well documented that some KATP channel modulators, such as nicorandil, pinacidil, and glibenclamide, regulate KATP channel activity by targeting the regulating subunit SUR (Gribble and Ashcroft, 2000a; Hansen, 2006), whereas others (e.g., ...
TY - JOUR. T1 - The KATP channel activator diazoxide ameliorates amyloid-β and Tau pathologies and improves memory in the 3xTgAD mouse model of Alzheimers disease. AU - Liu, Dong. AU - Pitta, Michael. AU - Lee, Jong Hwan. AU - Ray, Balmiki. AU - Lahiri, Debomoy. AU - Furukawa, Katsutoshi. AU - Mughal, Mohamed. AU - Jiang, Haiyang. AU - Villarreal, Julissa. AU - Cutler, Roy G.. AU - Greig, Nigel H.. AU - Mattson, Mark P.. PY - 2010. Y1 - 2010. N2 - Compromised cellular energy metabolism, cerebral hypoperfusion, and neuronal calcium dysregulation are involved in the pathological process of Alzheimers disease (AD). ATP-sensitive potassium (KATP) channels in plasma membrane and inner mitochondrial membrane play important roles in modulating neuronal excitability, cell survival, and cerebral vascular tone. To investigate the therapeutic potential of drugs that activate KATP channels in AD, we first characterized the effects of the KATP channel opener diazoxide on cultured neurons, and then ...
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 ...
TY - JOUR. T1 - Advances in cardiac ATP-Sensitive K + channelopathies from molecules to populations. AU - Terzic, Andre. AU - Alekseev, Alexey E.. AU - Yamada, Satsuki. AU - Reyes, Santiago. AU - Olson, Timothy Mark. PY - 2011/8. Y1 - 2011/8. N2 - Deficient cellular energetics set by aberrant K ATP channel function increasingly is implicated in a spectrum of conditions underlying metabolic imbalance and electric instability. 5 Indeed, cardiac K ATP channelopathies are emerging as a recognized disease entity underlying heart failure and arrhythmia. 19 Understanding the molecular structure and function of K ATP channel subunits, 8 and their relationship to cellular metabolic signaling, 99 has been instrumental in interpreting the pathophysiology of channel malfunction associated with heart disease predisposition (Figure 3). 12 From individual patients to populations, variants in K ATP channel genes now have been documented in human dilated cardiomyopathy 21 and atrial fibrillation 20 and as risk ...
BACKGROUND: Alterations in coronary vasomotor tone may participate in the pathogenesis of acute myocardial infarction (AMI). Vascular ATP-sensitive K(+) (KATP) channels, formed by Kir6.x/SUR2B, are key regulators of coronary tone and mutations in cardiac (Kir6.2/SUR2A) KATP channels result in heart disease. Here we explore the pathophysiological mechanism of a rare mutation (V734I) found in exon 17 of the ABCC9 gene, estimated to cause a 6.4-fold higher risk of AMI before the age of 60. METHODS AND RESULTS: Eleven patients carrying the mutation were identified; they presented AMI of vasospastic origin associated with increased plasma levels of endothelin-1 and increased leukocyte ROCK activity. The effects of the mutation on the functional properties of the two splice variants of ABCC9 (SUR2A and SUR2B) were studied using patch-clamp electrophysiology. The mutation reduced the sensitivity to MgATP inhibition of Kir6.2/SUR2B channels but not of Kir6.2/SUR2A and Kir6.1/SUR2B channels. Furthermore, the
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 ...
Extracellular Zn(2+) has been identified as an activator of pancreatic K(ATP) channels. We further examined the action of Zn(2+) on recombinant K(ATP) channels formed with the inward rectifier K(+) channel subunit Kir6.2 associated with either the pancreatic/neuronal sulphonylurea receptor 1 (SUR1) …
Most information currently available regarding vascular K+ channel function in diabetes concerns KATP channels. As for chronic hypertension, there are now several reports of impaired vascular relaxant responses to synthetic openers of KATP channels in long-term diabetes. These studies have mostly utilized the streptozotocin-injected rat model of diabetes and have examined vessels at 2.5 to 4 months after streptozotocin treatment. In this model in which plasma glucose levels are increased 3- to 4-fold, impaired relaxation of the isolated aorta122 123 124 and mesenteric vascular bed125 and reduced dilatation of large126 and small127 cerebral arteries in vivo typically develop. These changes are thought to be the result of a decreased number of vascular KATP channels and/or reduced sensitivity of these channels to synthetic openers. Nonspecific cytotoxic effects of streptozotocin seem an unlikely cause of these changes because, like other manifestations of vascular dysfunction, abnormal vasodilator ...
Most information currently available regarding vascular K+ channel function in diabetes concerns KATP channels. As for chronic hypertension, there are now several reports of impaired vascular relaxant responses to synthetic openers of KATP channels in long-term diabetes. These studies have mostly utilized the streptozotocin-injected rat model of diabetes and have examined vessels at 2.5 to 4 months after streptozotocin treatment. In this model in which plasma glucose levels are increased 3- to 4-fold, impaired relaxation of the isolated aorta122 123 124 and mesenteric vascular bed125 and reduced dilatation of large126 and small127 cerebral arteries in vivo typically develop. These changes are thought to be the result of a decreased number of vascular KATP channels and/or reduced sensitivity of these channels to synthetic openers. Nonspecific cytotoxic effects of streptozotocin seem an unlikely cause of these changes because, like other manifestations of vascular dysfunction, abnormal vasodilator ...
In the present study, the novel KATP channel antagonist HMR 1402 did not alter the cardiac action potential under control conditions but significantly attenuated the shortening of the APD90 induced either by the KATP channel agonist rilmakalim or by hypoxia. In a similar manner, the same concentration of this drug that attenuated these reductions in APD90 did not inhibit the activation of pancreatic or coronary vascular KATP channels in vitro. In conscious dogs, HMR 1402 prevented ischemically induced ventricular fibrillation without altering the increases in mean coronary blood flow induced either by submaximal exercise or by the reactive hyperemic response to brief (15-s) coronary artery occlusions. These findings were in marked contrast to glibenclamide that provoked large reductions in coronary blood flow (Billman et al., 1993, 1998). Finally, HMR 1402, in contrast to glibenclamide (Billman et al., 1998), did not alter plasma insulin concentrations. When considered together, these data ...
This study tests the hypothesis that glycolytic regulation of KATP channel activity is altered in myocardial hypertrophy. Left ventricular (LV) subendocardial myocytes were isolated from cats with normal or left ventricular hypertrophied hearts (LVH)
In addition to the pancreatic β-cell the KATP channel resides on smooth and cardiac muscles and other nonneural tissues. The KATP channel is present on brain GR neurons but not glia (20). The Kir6.2 pore-forming unit (20, 32, 35,63) and both a high (SUR1)- and low (SUR2)-affinity form of the SUR have been cloned and identified in brain (21, 33, 49, 51, 63, 114). A presumptive endogenous ligand for the SUR, α-endosulfine, was also identified in the brain (84) but little is known about its regulation or regional distribution. Similar to the pancreatic β-cell, the KATP channel on GR neurons is inactivated by an increased intracellular ATP-to-ADP ratio or the presence of sulfonylureas. This leads to accumulation of intracellular K+ with subsequent membrane depolarization and cell firing (6, 21, 87, 89). Although it is clear that GR neurons use glucose as a signaling molecule acting via the KATP channel, several unresolved issues remain. First, the neuronal glucose transporter (GLUT-3) (26) and ...
Recombinant KATP channels consisting of CFP-Kir6.2 or CFP-Kir6.2-YFP (Fig. 1A) with or without SUR1 or SUR2A were expressed in HEK cells and illuminated at 440 nm, the excitation wavelength of the donor fluorophore CFP. Fluorescence was recorded at both 535 nm, the peak emission wavelength of the acceptor fluorophore YFP, and at 480 nm, the peak emission wavelength of CFP. The extent of FRET was quantified as the fluorescence ratio F535/F480.. Figure 1B shows the F535/F480 ratio recorded for each combination of subunits studied. This value was negligible for CFP-Kir6.2 (which lacks the YFP fluorophore), demonstrating that our method of correction for CFP bleedthrough was effective. In contrast, cells expressing CFP-Kir6.2-YFP showed significant FRET (Fig. 2B). This result indicates that CFP and YFP lie within a few nanometers of each other. Because CFP is attached to the NH2-terminus of Kir6.2 and YFP to the COOH-terminus, the distal parts of the intracellular domains of Kir6.2 must also lie ...
The intersection of cell metabolism with electrical signaling links the environment and cell function over time scales ranging from milliseconds to lifetimes. In responding to cellular metabolites, adenosine triphosphate (ATP)-sensitive potassium (KATP) channels are an important component of this intersection. Recent studies have begun to delineate the roles of KATP channels in multiple tissues and the far-reaching consequences of aberrant KATP channel activity and disturbed sensing of cell metabolism.. ...
This is the Authors Original Manuscript of an article published by Taylor & Francis in Channels on 02 Jan 2018 available online: https://doi.org/10.1080/19336950.2017.1412151 ...
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TY - JOUR. T1 - Short-term effects of glipizide (an adenosine triphosphate-sensitive potassium channel inhibitor) on cardiopulmonary hemodynamics and global oxygen transport in healthy and endotoxemic sheep. AU - Lange, Matthias. AU - Szabo, Csaba. AU - Van Aken, Hugo. AU - Williams, William. AU - Traber, Daniel L.. AU - Daudel, Fritz. AU - Bröking, Katrin. AU - Salzman, Andrew L.. AU - Bone, Hans Georg. AU - Westphal, Martin. PY - 2006/11. Y1 - 2006/11. N2 - In severe sepsis and septic shock, hemodynamic support is often complicated by a tachyphylaxis against exogenous catecholamines. Because activation of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels plays a pivotal role in the pathogenesis of hyperdynamic vasodilatory shock, we hypothesized that it may be beneficial to administer a specific KATP channel inhibitor to prevent, or at least attenuate, hemodynamic dysfunction in sepsis. The present study was designed as a prospective and controlled laboratory experiment to ...
ATP-sensitive K+ (K(ATP)) channels are hetero-octamers of inwardly rectifying K+ channel (Kir6.2) and sulphonylurea receptor subunits (SUR1 in pancreatic beta-cells, SUR2A in heart). Heterozygous gain-of-function mutations in Kir6.2 cause neonatal diabetes, which may be accompanied by epilepsy and developmental delay. However, despite the importance of K(ATP) channels in the heart, patients have no obvious cardiac problems. We examined the effects of adenine nucleotides on K(ATP) channels containing wild-type or mutant (Q52R, R201H) Kir6.2 plus either SUR1 or SUR2A. In the absence of Mg2+, both mutations reduced ATP inhibition of SUR1- and SUR2A-containing channels to similar extents, but when Mg2+ was present ATP blocked mutant channels containing SUR1 much less than SUR2A channels. Mg-nucleotide activation of SUR1, but not SUR2A, channels was markedly increased by the R201H mutation. Both mutations also increased resting whole-cell K(ATP) currents through heterozygous SUR1-containing channels to a
TY - JOUR. T1 - Spontaneous contractions of the pig urinary bladder. T2 - The effect of ATP-sensitive potassium channels and the role of the mucosa. AU - Akino, Hironobu. AU - Chapple, Christopher R.. AU - McKay, Neil G.. AU - Cross, Rebecca L.. AU - Murakami, Shigetaka. AU - Yokoyama, Osamu. AU - Chess-Williams, Russell. AU - Sellers, Donna J.. PY - 2008/11. Y1 - 2008/11. N2 - OBJECTIVE: To investigate the influence of the mucosa on the inhibitory effects of the ATP-sensitive potassium channel (KATP channel) opener, cromakalim, on the spontaneous contractions of pig bladder strips from the bladder dome and trigone. Little is known about the influence of the mucosa on spontaneous contractions and whether the nature of these contractions differs between the bladder dome and trigone. MATERIALS AND METHODS: Paired longitudinal strips of female pig bladders were isolated from the dome and trigone. The mucosa was removed from one strip per pair and tissues were set up in organ baths. Spontaneous ...
In response to intracellular energy supply, ATP-sensitive potassium (KATP) channels alter membrane potential and mediate cell stress response. The Abcc9 gene encodes the major regulatory subunit in the heart, sulfonylurea receptor 2 (SUR2), as well as smaller mitochondria-enriched proteins that contribute to sulfonylurea-insensitive KATP channels. Pharmacological studies suggest mitochondrial KATP channels are critical regulators of cell stress, however the molecular composition of this channel has been unclear. We now studied the role of KATP channels by deleting exon 5 of Abcc9. This strategy ablated expression of both full length SUR2 protein as well as the smaller mitochondrial 55 KDa protein. Homozygous exon 5 (Ex5) mice died within 14 days of birth with progressive cardiac contractile dysfunction. Diazoxide was found to depolarize mitochondria from wildtype cardiomyocytes but not Ex5 mitochondria, consistent with disrupted mitochondrial KATP channels. Ex5 mitochondria had a reduced cross ...
The regulation of a K(+) current activating during oscillatory electrical activity (I(K,slow)) in an insulin-releasing beta-cell was studied by applying the perforated patch whole-cell technique to intact mouse pancreatic islets. The resting whole-cell conductance in the presence of 10 mM glucose amounted to 1.3 nS, which rose by 50 % during a series of 26 simulated action potentials. Application of the K(ATP)-channel blocker tolbutamide produced uninterrupted action potential firing and reduced I(K,slow) by approximately 50 %. Increasing glucose from 15 to 30 mM, which likewise converted oscillatory electrical activity into continuous action potential firing, reduced I(K,slow) by approximately 30 % whilst not affecting the resting conductance. Action potential firing may culminate in opening of K(ATP) channels by activation of ATP-dependent Ca(2+) pumping as suggested by the observation that the sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor thapsigargin (4 microM) inhibited I(K,slow) by
TY - JOUR. T1 - Hydrochlorothiazide: An hyperglycaemia-inducing agent and K-ATP channel agonist in human beta-cells and clonal insulin-secreting cells.. AU - Barnes, PD. AU - OBrien, RE. AU - Abdel-Wahab, Yasser. AU - Cosgrove, KE. AU - Flatt, Peter. AU - Dunne, MJ. PY - 1999/8. Y1 - 1999/8. M3 - Article. VL - 42. SP - 482. JO - Diabetologia. JF - Diabetologia. SN - 0012-186X. IS - Suppl.. ER - ...
TY - JOUR. T1 - Autocrine insulin increases plasma membrane KATP channel via PI3K-VAMP2 pathway in MIN6 cells. AU - Xu, Shanhua. AU - Kim, Ji Hee. AU - Hwang, Kyu Hee. AU - Das, Ranjan. AU - Quan, Xianglan. AU - Nguyen, Tuyet Thi. AU - Kim, Soo Jin. AU - Cha, Seung Kuy. AU - Park, Kyu Sang. PY - 2015/12/25. Y1 - 2015/12/25. N2 - Regulation of ATP-sensitive inwardly rectifying potassium (KATP) channel plays a critical role in metabolism-secretion coupling of pancreatic β-cells. Released insulin from β-cells inhibits insulin and glucagon secretion with autocrine and paracrine modes. However, molecular mechanism by which insulin inhibits hormone secretion remains elusive. Here, we investigated the effect of autocrine insulin on surface abundance of KATP channel in mouse clonal β-cell line, MIN6. High glucose increased plasmalemmal sulfonylurea receptor 1 (SUR1), a component of KATP channel as well as exogenous insulin treatment. SUR1 trafficking by high glucose or insulin was blocked by ...
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 ...
Among the several ion channels expressed in skeletal muscle, this laboratory has largely focused on the ATP-sensitive K + channel or KATP channel. This channel is interesting because its activity is regulated by the energy state of the muscle fibers, where a decrease in energy reserve increases the activity of the channel. It therefore behaves as an energy sensor. Being an ion channel, it is also an effector, which links the energy state of the fiber to the electrical activity of the cell membrane.. Our studies have now clearly demonstrated that the KATP channel is crucial in preventing fiber damage during treadmill running and fatigue elicited in vitro (References #4-5). We are in the process of elucidating two major mechanisms of action for the channel. The first mechanism involves a reduction in action potential amplitude (Reference #6). As a consequence of lower action potential amplitude, less Ca 2+ is released by the sarcoplasmic reticulum and less force is developed by the contractile ...
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In experiments on the anaesthetized dogs the influence of a new fluorine-containing opener of ATP-sensitive potassium (K(ATP)) channels flocalin on the cardiohemodynamic of great animals in vivo was studied. Flocalin introduced intravenously in doses 0.01 - 1.5 mgs/kg. It is shown that it reduces in dose-dependent manner a system arterial pressure, perfusion pressure in coronary artery and general peripheral resistance of vessels with maximal effects on 56.8 +/- 2.7, 22.4 +/- 4.7 and 47.2% +/- 6.5% accordingly at most dose 1.5 mgs/kg. Flocalin causes development of cardiodepressive reactions in heart, that is exhibited in dose-dependent the decrease of pressure in the left ventricle, speed of growth (dP/dt(max)) and reduction (dP/dt(min)) in its of pressure with maximal effects on 37.1 +/- 5.1, 51.2 +/- 9.4 and 55.6% +/- 6.9% accordingly at introduction of most dose of flocalin. Diminish of the cardiac out put and heart rate with a maximal effects on 23.1% +/-12.7% and 19.2% +/- 1.7% ...
心不全によるK_,ATP,チャネルの変調 : レシピエントから得た心筋による検討 Alterations in ATP-sensitive potassium channel sensitivity to ATP in failing human hearts ...
Propofol reportedly possesses potential antioxidant properties caused by its chemical structure similar to that of phenol-based free-radical scavengers such as vitamin E.10 Previous in vivo or in vitro studies documented that this intravenous anesthetic reduces oxidative stress toward blood vessels.11,12 These results suggest that this anesthetic may be protective against the vascular dysfunction caused by increased oxidative stress. Indeed, propofol (3 × 10−7to 10−6m) recovered vascular ATP-sensitive K+channel function via reduction of superoxide levels within arterial walls. In addition, 10−6m of this agent completely inhibited protein expression of a Nox2-related NADPH oxidase subunit p47phox. The plasma concentration of propofol during induction of anesthesia in humans has been reported as up to 3 × 10−5m, and burst suppression doses of propofol for cerebral protection are up to 6 × 10−5m.20-22 Effective concentrations of propofol (3 × 10−7to 10−6m) to inhibit NADPH oxidase ...
Endotoxemia causes hypotension characterized by vasodilation and resistance to vasopressor agents. The molecular mechanisms responsible for these changes are unclear. The ATP-regulated K+ (K+ATP) channel has recently been found to be an important modulator of vascular smooth muscle tone which may transduce local metabolic changes into alterations of vascular flow. We report here that in endotoxic hypotension, the sulfonylurea glyburide, a specific inhibitor for the K+ATP channel, caused vasoconstriction and restoration of blood pressure. Glyburide also induced vasoconstriction and restoration of blood pressure in the vasodilatory hypotension caused by hypoxic lactic acidosis, while it was ineffective in the hypotension induced by sodium nitroprusside. Thus, vasodilation and hypotension in septic shock are, at least in part, due to activation of the K+ATP channel in vascular smooth muscle, and anaerobic metabolism with acidosis is a sufficient stimulus for channel activation. Because anaerobic ...
Consistent with the report by Han et al. ,22 the single-channel conductance was not altered by isoflurane in our study. However, in contrast to findings in other species,22,24 application of isoflurane to the inside-out membrane patches from rat non-APC myocytes increased the probability of channel opening. Characteristically, Po was increased during exposure to isoflurane but declined upon anesthetic washout. Because single-channel recordings were made at intracellular pH 7.2, which is in the range of normal physiologic intracellular pH in rat cardiomyocytes,25 the effect of isoflurane on channel activity in rats seems different from those in guinea pigs, where isoflurane increased Po only at more acidic, ischemic-like pH of 6.8,23 and in rabbits where isoflurane clearly had an inhibitory effect on Po at intracellular pH of 7.4.22 The in vivo APC in rats produced no lasting change in channel activity, and Po values of channels in APC and non-APC myocytes were similar. The observation that Po of ...
We found in the present study that ICV injections of glibenclamide produced a dose-dependent pressor effect in rats with bilateral ligation of the carotid arteries but not in sham-operated rats. Because glibenclamide is a specific and potent blocker of KATP18 and because intravenous administration of glibenclamide did not elicit any cardiovascular response in rats with bilateral ligation of the carotid arteries, this pressor effect must be closely related to inhibition of KATP in the ischemic brain. Intravenous glibenclamide can reach the brain after bilateral ligation of the carotid artery because the residual blood flow still exists, although the amount of glibenclamide must be lower than the ICV injection because of the dilution with blood. A lack of vasopressor effects with intravenous injections of glibenclamide suggests that a large amount of glibenclamide is needed to inhibit KATP in rat brain. Otherwise, glibenclamide may not penetrate the blood-brain barrier.. Although KATP in the ...
AMP-activated protein kinase connects cellular energy metabolism to KATP channel function. J Mol Cell Cardiol. 2012 Feb; 52(2):410-8 ...
Shaker-type, voltage-gated K+ (KV1) channels are an important determinant of the resting membrane potential and diameter of small cerebral arteries. During hype...
Differences in the mechanism of metabolic regulation of ATP-sensitive K+ channels containing Kir6.1 and Kir6.2 subunits.: Kir6.1\SUR2B has intrinsic sensitivity
Hari ni Ida nk tayang sayur petola ular goreng... pernah makan ke sayur petola ular ni? mana la tau kot2 dengar nama pun dh geli.. hehehe.. Ida jarang2 je makan.. tu pun kalau my mom beli.. tapi sekali sekala makan sedap jugak.. tak cukup dibuatnya heheheh ...
H. Huopio1, S.-L. Shyng, T. Otonkoski3, and C. G. Nichols4 (2002-08-01). "KATP channels and insulin secretion disorders". ...
A Promising KATP Channel Activating Agent". Cardiovascular Drug Reviews. 18: 25. doi:10.1111/j.1527-3466.2000.tb00031.x. v t e ... Bimakalim is a potassium channel opener. Puddu, Paolo Emilio; Garlid, Keith D; Monti, Francesco; Iwashiro, Katsunori; Picard, ... Potassium channel openers, 2-Pyridones, Benzopyrans, Nitriles, All stub articles, Cardiovascular system drug stubs). ...
An ATP-sensitive potassium channel (or KATP channel) is a type of potassium channel that is gated by intracellular nucleotides ... and the ATP/ADP ratio determines KATP channel activity. Under resting conditions, the weakly inwardly rectifying KATP channels ... the KATP channels close, causing the membrane potential of the cell to depolarize, activating voltage-gated calcium channels, ... similar to plasma membrane KATP channels. Four genes have been identified as members of the KATP gene family. The sur1 and ...
Both genes encode in ATP sensitive potassium (KATP) channel subunits. This second gene is also located on the short arm of ... Nichols, Colin G.; Singh, Gautam K.; Grange, Dorothy K. (2013-03-29). "KATP channels and cardiovascular disease: Suddenly a ... causes inhibition of voltage-gated potassium channels and contraction of smooth muscle (in ductus). This condition can be ...
He was instrumental in cloning the first inward rectifier channel and the regulatory subunit of the KATP channel. He elucidated ... Koster, J.; Marshall, B.A.; Ensor, N.; Corbett, J.A.; Nichols, C.G. (2000). "Targeted Overactivity of β Cell KATP Channels ... Colin Nichols elected to Royal Society, WUSTL Newsroom 2014-06-27 Nichols, C. G. (2006). "KATP channels as molecular sensors of ... Nichol's research investigates the biology of ion channels, particularly potassium channels, and their role in diabetes ...
Hence, the KATP channel monitors the energy balance within the cell. Depending on the tissue in which the KATP channel is ... The association of four Kir6.x and four SUR subunits form an ion conducting channel commonly referred to as the KATP channel. ... binds to the KATP channel resulting in channel closure. The relative depolarization (decrease in membrane hyperpolarization), ... Under cerebral ischemic conditions, SUR1, the regulatory subunit of the KATP and the NCCa-ATP channels, is expressed in neurons ...
Since KATP channels only become activated during periods of low ATP and High ADP, HMR 1883 only affects hypoxic tissue and has ... Activation of the KATP channels on cardiac mitochondria is involved in ischemic preconditioning that results in protection for ... Cardioselective KATP Channel Blockers Derived from a New Series of m-Anisamidoethylbenzenesulfonylthioureas J. Med. Chem. 44 (7 ... HMR 1098 is not an SUR isotype specific inhibitor of heterologous or sarcolemmal KATP channels. J. Mol. Cell. Cardiol. 50(3): ...
2004). "Syntaxin-1A inhibits cardiac KATP channels by its actions on nucleotide binding folds 1 and 2 of sulfonylurea receptor ... 2003). "Molecular basis and characteristics of KATP channel in human corporal smooth muscle cells". Int. J. Impot. Res. 15 (4 ... and its regulation of the KATP channel". Circ. Res. 102 (2): 164-76. doi:10.1161/CIRCRESAHA.107.165324. PMID 18239147. Ellis JA ... "Toward understanding the assembly and structure of KATP channels". Physiol. Rev. 78 (1): 227-45. doi:10.1152/physrev.1998.78. ...
It may be associated with ATP-sensitive K+ (KATP) channels. AGN 192403Moxonidine CR-4056 Phenyzoline (2-(2-phenylethyl)-4,5- ...
Zhuo ML, Huang Y, Liu DP, Liang CC (April 2005). "KATP channel: relation with cell metabolism and role in the cardiovascular ... Ashford ML, Bond CT, Blair TA, Adelman JP (1996). "Cloning and functional expression of a rat heart KATP channel". Nature. 378 ... Tucker SJ, James MR, Adelman JP (July 1995). "Assignment of KATP-1, the cardiac ATP-sensitive potassium channel gene (KCNJ5), ... G protein-coupled inwardly-rectifying potassium channel Inward-rectifier potassium ion channel GRCh38: Ensembl release 89: ...
Gloyn AL, Siddiqui J, Ellard S (2006). "Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 ( ... Kir6.2 is a major subunit of the ATP-sensitive K+ channel, a lipid-gated inward-rectifier potassium ion channel. The gene ... "Molecular cell biology of KATP channels: implications for neonatal diabetes". Expert Rev Mol Med. 9 (21): 1-17. doi:10.1017/ ... Inward-rectifier potassium ion channel Potassium channel GRCh38: Ensembl release 89: ENSG00000187486 - Ensembl, May 2017 GRCm38 ...
In cardiac myocytes, caveolin-3 negatively regulates ATP-dependent potassium channels (KATP) localized in caveolae. KATP ... other isoforms of caveolin do not show this type of effect on KATP channels. The amount of KATP activation during times of ... Caveolin-3 influences the opening of L-Type calcium channels (LTCC) which play a role in cardiac myocyte contraction. ... Garg V, Sun W, Hu K (2009). "Caveolin-3 negatively regulates recombinant cardiac K(ATP) channels". Biochem. Biophys. Res. ...
... sees that channel trafficking requires KATP channels need the shielding of ER retention signal.E282K prevents the KATP channel ... is needed in KATP channel mechanism.R1215Q mutations (ABCC8 gene) affect ADP gating which in turn inhibits KATP channel. In ... Diazoxide works by opening the KATP channels of the beta cells. Octreotide must be given by injection several times a day or a ... especially those involving abnormalities of KATP channel function, can worsen or improve with time. The potential harm from ...
The PKC is presumably phosphorylating the KATP channel instead of ATP. The stonefish, Synanceia verrucosa, has a diverse set of ... Verrucotoxin has been studied to interact with both calcium ion channels and potassium ATP channels. The calcium ion channel is ... Wang, Jian-Wu; Yazawa, Kazuto; Hao, Li-Ying; Onoue, Yoshio; Kameyama, Masaki (June 2007). "Verrucotoxin inhibits KATP channels ... Ichthyotoxins, Potassium channel blockers, Calcium channel openers, Glycoproteins). ...
ABCC8 is the regulatory subunit of the ATP-sensitive potassium (KATP) channel, which is located on the plasma membrane of ... This protein is thought to be an endogenous regulator of KATP channels. In vitro studies have demonstrated that this protein ... a possible regulator of sulfonylurea-sensitive KATP channel: Molecular cloning, expression and biological properties". Proc ... modulates insulin secretion through the interaction with KATP channel, and this gene has been proposed as a candidate gene for ...
"Titration of KATP channel expression in mammalian cells utilizing recombinant baculovirus transduction". Receptors & Channels. ... Receptors and Channels. 10 (3-4): 117-124. doi:10.1080/10606820490515012. PMID 15512846. Cheng, T; Xu, CY; Wang, YB; Chen, M; ... Receptors and Channels. 10 (3-4): 99-107. doi:10.1080/10606820490514969. PMID 15512844. Ames, Robert S; Kost, Thomas A; ...
"Ketogenic Diet Metabolites Reduce Firing in Central Neurons by Opening KATP Channels". The Journal of Neuroscience. 27 (14): ...
Sulfonylureas are effective in the KATP channel forms of neonatal-onset diabetes. The mouse model of MODY diabetes suggested ...
MLC901 can activate KATP channels, which has a neuroprotective effect against brain ischemia. Neuroaid is not effective in ...
1999). "Block of human aorta Kir6.1 by the vascular KATP channel inhibitor U37883A". Br. J. Pharmacol. 128 (3): 667-672. doi: ... 2003). "Molecular basis and characteristics of KATP channel in human corporal smooth muscle cells". Int. J. Impot. Res. 15 (4 ... 2001). "Pharmacological comparison of native mitochondrial K(ATP) channels with molecularly defined surface K(ATP) channels". ... Potassium inwardly-rectifying channel, subfamily J, member 8, also known as KCNJ8, is a human gene encoding the Kir6.1 protein ...
... is also the ATP-sensitive potassium channel responsible for pancreatic beta-cell insulin release. KATP (101.9 FM, "The ... 2017 101.9 The Bull KATP in the FCC FM station database KATP on Radio-Locator KATP in Nielsen Audio's FM station database ... On March 27, 2017, KATP rebranded from "Blake FM" to "101.9 The Bull". Blake FM Leave Behind a Bull in Amarillo Radioinsight - ...
"Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel ... FHI-GCK, caused by mutations in GCK, may be much milder than FHI-KATP; however, some persons have severe, diazoxide- ... Individuals with autosomal dominant FHI-KATP tend to be appropriate for gestational age at birth, to present at approximately ... Individuals with autosomal recessive familial hyperinsulinism, caused by mutations in either ABCC8 or KCNJ11 (FHI-KATP), tend ...
Gross ER, Hsu AK, Gross GJ (July 2007). "GSK3β inhibition and KATP channel opening mediate acute opioid-induced ...
"Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel ...
Ashcroft's research focuses on ATP-sensitive potassium (KATP)channels and their role in insulin secretion. Ashcroft is working ... Ashcroft has authored a few science and popular science books based on ion channel physiology: Ion Channels and Disease: ... Ashcroft is a director of Oxion: Ion Channels and Disease Initiative, a research and training programme on integrative ion ... Dame Frances Mary Ashcroft DBE FRS FMedSci (born 1952) is a British ion channel physiologist. She is Royal Society ...
"Loss of functional KATP channels in pancreatic β-cells causes persistent hyperinsulinemic hypoglycemia of infancy". Nature ...
"Ventricular fibrillation with prominent early repolarization associated with a rare variant of KCNJ8/KATP channel". Journal of ... It is thought the causing mechanism of early repolarization is a more excitable ion channel system, which causes a quicker ... October 2010). "Gain-of-function mutation S422L in the KCNJ8-encoded cardiac K(ATP) channel Kir6.1 as a pathogenic substrate ... Genes associated with ER and ATP sensitive potassium current channel mutations are KCNJ8, ABCC9 Others associated with ...
KATP. Disease-associated variants of either subunit of KATP, KCNJ11 and ABCC8, can result in a channel that is "stuck open", ... NDM is not initiated by an autoimmune mechanism but mutations in KATP-sensitive channel, KCNJ11, ABCC8 and INS genes are ... all due to the presence of KATP channels in the brain. These can range from unnoticably mild to severe, and can sometimes ... People with KATP channel variations are at increased risk of developing attention deficit hyperactivity disorder, sleep ...
... a possible regulator of sulfonylurea-sensitive KATP channel: molecular cloning, expression and biological properties". Proc. ...
They are insulin secretagogues, triggering insulin release by inhibiting the KATP channel of the pancreatic beta cells. Eight ... By closing the potassium channels of the pancreatic beta cells, they open the calcium channels, thereby enhancing insulin ... They act on the same potassium channels as sulfonylureas, but at a different binding site. ...
"Isolation of a cDNA clone encoding a KATP channel-like protein expressed in insulin-secreting cells, localization of the human ... G protein-coupled inwardly-rectifying potassium channel Inward-rectifier potassium ion channel GRCh38: Ensembl release 89: ... "Characterization and variation of a human inwardly-rectifying-K-channel gene (KCNJ6): a putative ATP-sensitive K-channel ... G protein-activated inward rectifier potassium channel 2 is a protein that in humans is encoded by the KCNJ6 gene. Mutation in ...
June 2008). "Elimination of KATP Channels in Mouse Islets Results in Elevated U-13CGlucose Metabolism, Glutaminolysis, and ...
KATP, BK, IK, CLIC5, Kv7.4 at the inner membrane and VDAC and CLIC4 as outer membrane channels. Some ion channels are ... Sodium channels Voltage-gated sodium channels (NaVs) Epithelial sodium channels (ENaCs) Calcium channels (CaVs) Proton channels ... Plasma membrane channels Examples: Voltage-gated potassium channels (Kv), Sodium channels (Nav), Calcium channels (Cav) and ... Ion channels may be classified by gating, i.e. what opens and closes the channels. For example, voltage-gated ion channels open ...
KXSS, along with its sister stations KPRF-FM, KATP-FM, KMXJ-FM, and KIXZ, was acquired along with approximately fifty other ... The 96.9 frequency was, until 2008, home to a country music format as "96.9 KMML," under the ownership of Clear Channel ... Communications; however, it was one of close to 450 radio stations sold by Clear Channel in the process of privatization, ...
KATP channel closure, and the opening of voltage gated calcium channels causing insulin granule fusion and exocytosis. Voltage- ... These ATP-sensitive potassium ion channels are normally open and the calcium ion channels are normally closed. Potassium ions ... gated calcium channels and ATP-sensitive potassium ion channels are embedded in the plasma membrane of beta cells. ... The ATP-sensitive potassium ion channels close when this ratio rises. This means that potassium ions can no longer diffuse out ...
... has made many significant contributions to physiology including the discovery of the KATP ion channel. "Akinori ... Noma, A. (1983). "ATP-regulated K+ channels in cardiac muscle". Nature. 305 (5930): 147-148. doi:10.1038/305147a0. PMID 6310409 ...
Moreover, under ischemic conditions SUR1, the regulatory subunit of the KATP- and the NCCa-ATP-channels, is expressed in ... The medication works by binding to and inhibiting the ATP-sensitive potassium channels (KATP) inhibitory regulatory subunit ... Serrano-Martín X, Payares G, Mendoza-León A (December 2006). "Glibenclamide, a blocker of K+(ATP) channels, shows ... This inhibition causes cell membrane depolarization, opening voltage-dependent calcium channels.[medical citation needed] This ...
They bind to an ATP-dependent K+ (KATP) channel on the cell membrane of pancreatic beta cells in a similar manner to ... This depolarization opens voltage-gated Ca2+ channels. The rise in intracellular calcium leads to increased fusion of insulin ...
Wulfkuhle, Virginia A. "KATP Field School Will Uncover New Information at Pawnee Indian Museum State Historic Site". Kansas ... from the bank's base to the present channel. The remains of over 100 earth lodges lie on the terrace between the bank and hills ...
"Exploitation of the KATP Channel Opener Diazoxide during Cardiac Surgery." During her tenure at the Washington University ...
Kim, SJ; Lee, YJ; Kim, JB (Jan 2010). "Reduced expression and abnormal localization of the KATP channel subunit SUR2A in ... Voltage-gated sodium channel (Nav1.4) mutations are among the key causes behind periodic paralysis. Hyper-kalemic PP (hyperPP) ... The underlying mechanism of these diseases are malfunctions in the ion channels in skeletal muscle cell membranes that allow ... Imparts pH-Sensitivity in Skeletal Muscle Voltage-gated Sodium Channels". Scientific Reports. 8 (1): 13. Bibcode:2018NatSR... ...
... activates KATP channels in the mitochondria of the myocardium, which appears to relay the cardioprotective effects, ... Studies show that this is due to its KATP channel agonist action which causes pharmacological preconditioning and provides ... PKG acts on K+ channels to promote K+ efflux and the ensuing hyperpolarization inhibits voltage-gated calcium channels. Overall ... which is associated with increased ATP-sensitive K+ channel (KATP) opening. Nicorandil stimulates guanylate cyclase to increase ...
... which codes for the Kir6.2 subunit of the beta cell KATP channel. This disease is considered to be a type of maturity onset ...
KATP channel disorders) Paternal SUR1 mutation with clonal loss of heterozygosity of 11p15 Paternal Kir6.2 mutation with clonal ... loss of heterozygosity of 11p15 Diffuse hyperinsulinism KATP channel disorders SUR1 mutations Kir6.2 mutations Glucokinase gain ...
Insulin signaling activates the adenosine triphosphate (ATP)-sensitive potassium (KATP) channels in the arcuate nucleus, ... channels control hepatic glucose production". Nature. 434 (7036): 1026-31. Bibcode:2005Natur.434.1026P. doi:10.1038/nature03439 ...
... is thought to stimulate insulin secretion by closing the ATP-sensitive potassium KATP channels in pancreatic β ...
... therefore no increase in ATP concentration which is required to close the KATP channel in the beta cells of the pancreas ...
... to predict the extent of sulphonylurea inhibition of KATP channels at therapeutic concentrations in vivo. KATP currents from ... In contrast, the free gliclazide concentration in plasma is high enough to close KATP channels and stimulate insulin secretion. ... We therefore measured the ability of gliclazide and glibenclamide to inhibit KATP channels and stimulate insulin secretion in ... In contrast, glibenclamide inhibition of recombinant KATP channels was dramatically suppressed by albumin (predicted free drug ...
4. Thus, myocyte-KATP channels play a negligible role modulating intact in vivo cardiac contraction or arrhythmia in normal and ... 4. Thus, myocyte-KATP channels play a negligible role modulating intact in vivo cardiac contraction or arrhythmia in normal and ... 4. Thus, myocyte-KATP channels play a negligible role modulating intact in vivo cardiac contraction or arrhythmia in normal and ... Cardiomyocyte KATP channels were inhibited by HMR 1098, and data obtained under basal conditions, during epinephrine infusion ...
K-atp channel closes and increases k+ within cell causing depolarisation and... ... What does K-ATP channel do in beta cells when ATP increases within cell? A. ... A. K-atp channel closes and increases k+ within cell causing depolarisation and insulin release. B. K-atp channel closes and ... C. K-atp channel opens and increases k+ within cell causing depolarisation and insulin release. D. K-atp channel opens and ...
Glimepiride block of Kir6.2/SUR1 Kir6.2/SUR2A and Kir6.2/SUR2A and Kir6.2/SUR2B K-ATP channels. ... Glimepiride block of Kir6.2/SUR1 Kir6.2/SUR2A and Kir6.2/SUR2A and Kir6.2/SUR2B K-ATP channels. ...
... channels greatly improves postischemic myocardial recovery, the final effector mechanism for KATP channel-induced ... channels greatly improves postischemic myocardial recovery, the final effector mechanism for KATP channel-induced ... channels greatly improves postischemic myocardial recovery, the final effector mechanism for KATP channel-induced ... RhoA is a GTPase that regulates a variety of cellular processes known to be involved with KATP channel cardioprotection. Our ...
The KCNJ5 gene provides instructions for making a protein that functions as a potassium channel, which means that it transports ... G protein-activated inward rectifier potassium channel 4. *GIRK4. *heart KATP channel ... in the potassium channel. The altered potassium channels are less selective, allowing other ions, particularly sodium, to pass ... Potassium channels produced from the KCNJ5 gene are found in several tissues, including the adrenal glands, which are small ...
Effect of KATP channel openers on myogenic and neurogenic responses in goat urinary bladder. Indian Journal of Experimental ... KATP-channel openers namely, cromakalim or pinacidil (10(-7) - 10(-4) M) added cumulatively, elicited a concentration-related ... Effect of KATP channel openers on myogenic and neurogenic responses in goat urinary bladder. ... Glibenclamide, a KATP-channel blocker inhibited the cromakalim-induced concentration-related relaxation of spontaneous ...
The role of K ATP channels in cerebral ischemic stroke and diabetes ... Keywords: potassium channels; KATP channels; KATP channel blockers; sulfonylurea; stroke; diabetes ... KATP channels play important roles in controlling and regulating cellular functions in response to metabolic state, which are ... The role of KATP channels in cerebral ischemic stroke and diabetes Vivian SZETO1, Nai-hong CHEN2, Hong-shuo SUN1,3,4, Zhong- ...
... but when Mg2+ was present ATP blocked mutant channels containing SUR1 much less than SUR2A channels. Mg-nucleotide activation ... currents through heterozygous SUR1-containing channels to a greater extent than for heterozygous SUR2A-containing channels. The ... However, despite the importance of K(ATP) channels in the heart, patients have no obvious cardiac problems. We examined the ... In the absence of Mg2+, both mutations reduced ATP inhibition of SUR1- and SUR2A-containing channels to similar extents, ...
Ocular Hypotensive Properties and Biochemical Profile of QLS-101, a Novel ATP-Sensitive Potassium (KATP) Channel Opening ... Ocular Hypotensive Properties and Biochemical Profile of QLS-101, a Novel ATP-Sensitive Potassium (KATP) Channel Opening ...
KATP) channels. The authors have previously shown that isoflurane enhances sensitivity of the sarcolemmal KATP channel to the ... A possible role of the mitochondrial KATP channels was tested using a blocker of these channels, 5-hydroxydecanoate. ResultsThe ... myocytes were isolated from guinea pig hearts for the whole cell patch clamp recordings of the sarcolemmal KATP channel current ... that reactive oxygen species contribute to the mechanism by which isoflurane sensitizes the cardiac sarcolemmal KATP channel to ...
KATP Channels Katz Adjustment Scales use Psychiatric Status Rating Scales Kava Kava-Kava use Piper methysticum (Homeopathy) ... Kv1.6 Potassium Channel Kv3.1 Potassium Channel use Shaw Potassium Channels Kv3.2 Potassium Channel use Shaw Potassium Channels ...
Satake N, Shibata M. The involvement of KCa, KATP and Kv channels in vasorelaxing responses to acetylcholine in rat aortic ... The involvement of KCa, KATP and Kv channels in vasorelaxing responses to acetylcholine in rat aortic rings. / Satake, N.; ... Satake, N & Shibata, M 1997, The involvement of KCa, KATP and Kv channels in vasorelaxing responses to acetylcholine in rat ... Satake, N. ; Shibata, M. / The involvement of KCa, KATP and Kv channels in vasorelaxing responses to acetylcholine in rat ...
Molecular basis and structural insight of vascular KATP channel gating by s-glutathionylationexternal icon. Yang Y, Shi W, Chen ...
Hydrogen sulfide opens the KATP channel on rat atrial and ventricular myocytes. Cardiology 115, 120-126 (2010). ... Alpha lipoic acid protects the heart against myocardial post ischemia-reperfusion arrhythmias via KATP channel activation in ... Hydrogen sulfide inhibited L-type calcium channels (CaV1.2) via up-regulation of the channel sulfhydration in vascular smooth ... Interaction between hydrogen sulfide-induced sulfhydration and tyrosine nitration in the KATP channel complex. Am. J. Physiol. ...
Novel dominant KATP channel mutations in infants with congenital hyperinsulinism: Validation by in vitro expression studies and ... Leptin-induced Trafficking of KATP Channels: A Mechanism to Regulate Pancreatic β-cell Excitability and Insulin Secretion. Int ... Mechanism of pharmacochaperoning in a mammalian KATP channel revealed by cryo-EM. Elife. 2019 Jul 25;8:e46417. ... Sung MW, Yang Z, Driggers CM, Patton BL, Mostofian B, Russo JD, Zuckerman DM, Shyng SL. Vascular KATP channel structural ...
KATP binds nucleotides (Usher et al. 2021). Mitochondrial KATP channels stabilize intracellular Ca2+ during hypoxia in retinal ... KATP channels are metabolic sensors that couple cell energetics to membrane excitability. In pancreatic beta-cells, channels ... Channel closure is facilitated by ATP, which binds to the pore-forming subunit (Kir6.2). Conversely, channel opening is ... Many mutations in SUR1 render the channel unable to traffic to the cell surface, thereby reducing channel function. Many ...
Description: Vascular Kir6 (KATP) channel blocker Chemical Name: N-Cyclohexyl-N-tricyclo[,7]dec-1-yl-4- ... Different molecular sites of action for the KATP channel inhibitors, PNU-99963 and PNU-37883A. Cui et al.. Br.J.Pharmacol., ... Molecular analysis of the subtype-selective inhibition of cloned KATP channels by PNU-37883A. Kovalev et al.. Br.J.Pharmacol., ... PNU 37883 hydrochloride is a novel antagonist selective for the vascular form of Kir6 (KATP) channel; inhibits Kir6 currents in ...
KATP) channels have a regulatory effect on them. AIM: Investigation of the effects of KATP channel modulators,.. ... Effect of atp-sensitive potassium channel modulators on gastric lesions induced by indomethacin. *In: Academic Pharmacy Section ...
K-ATP ... channel ...
KATP channels and insulin secretion KATP channels and insulin secretion 50 min ... a training and research programme on the integrative physiology of ion channels. ...
Furthermore, GE uses the ATP-sensitive potassium (KATP) channel to sense glucose, as occurs in beta-cells. However, while KATP ... Fioramonti X, Lorsignol A, Taupignon A, Penicaud L. A new ATP-sensitive K+ channel-independent mechanism is involved in glucose ... Glucose-induced excitation of hypothalamic neurones is mediated by ATP-sensitive K+ channels. Pflugers Arch1990 Jan;415(4):479- ... channels are expressed in all GE neurons, only approximately half of VMH GE neurons express glucokinase, and approximately 30% ...
... channel plays a vitally important role in regulating insulin secretion and show how mutations in KATP channel genes can cause ... Add to Calendar 05/29/13 06:30 PM 05/29/13 07:30 PM United Kingdom (GMT) From bench to bedside: KATP channels and neonatal ... It will also reveal how an understanding of KATP channel function has led to a new therapy for patients with neonatal diabetes. ... Professor Ashcrofts research focuses on ion channels and their role in insulin secretion. She was awarded the Croonian Lecture ...
Ashcroft FM, Rorsman P. KATP channels and islet hormone secretion: new insights and controversies. Nat Rev Endocrinol. 2013;9( ... K+ channels. insulin secretion↑. hypoglycemia. weight gain. [100, 101, 114]. TZDs. Troglitazone/. Roziglitazone/. Pioglitazone ... Among these susceptible loci, KCNJ11 encodes the islet ATP-sensitive potassium channel Kir6.2; TCF7L2 regulates proglucagon ... Examples of candidate genes are KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11), TCF7L2 (transcription ...
Ligand-insensitive state of cardiac ATP-sensitive K+ channels: Basis for channel opening. Alekseev, A. E., Brady, P. A. & ... KATP channel dependent heart multiome atlas. Arrell, D. K., Park, S., Yamada, S., Alekseev, A. E., Garmany, A., Jeon, R., ... KATP channel pharmacogenomics: From bench to bedside. Sattiraju, S., Reyes, S., Kane, G. C. & Terzic, A., Feb 2008, In: ... KATP channel mutation confers risk for vein of Marshall adrenergic atrial fibrillation. Olson, T. M., Alekseev, A. E., Moreau, ...
PANCREATIC BETA-CELLS; K-ATP CHANNELS; ENDOPLASMIC-RETICULUM; CA2+ CONCENTRATION; DELTA-CELLS; INSULIN; SOMATOSTATIN; RELEASE; ... a-Cell K s i m ., was decreased by small-conductance Caactivated K+ (SK) channel inhibitors apamin and UCL 1684. ... Glucose-mediated inhibition of calcium-activated potassium channels limits α-cell calcium influx and glucagon secretion ... largeconductance Ca2+-activated K+ (BK) channel inhibitor iberiotoxin (IbTx), and intermediate-conductance Ca2+-activated K+ ( ...
Probing the Putative Role of KATP Channels and Biological Variability in a Mathematical Model of Chondrocyte Electrophysiology ...
Mitochondrial KATP channels contribute to the protective effects of hydrogen sulfide against impairment of central ...
KATP channel blocker; inhibits SUR1 €50.00 3503 Glipizide KATP channel blocker; inhibits SUR1 €50.00 ... KCNQ2/KCNQ3 channel opener; Anti-convulsant €80.00 3495 Ivabradine hydrochloride Selective sinus node I(f) channel inhibitor € ... Kv1.3 potassium channel blocker €110.00 3032 LUF7244 Potent negative allosteric modulator (NAM) of the Kv11.1 (hERG) channel € ... K+ channel opener (Ca2+ activated) €50.00 3019 A2764 dihydrochloride Selective inhibitor of the TRESK potassium channel €105.00 ...
  • Recently accumulated evidence underscoring the importance of mitochondria, reactive oxygen species, and KATP channels in cardioprotective signaling by volatile anesthetics is reviewed, and current concepts and controversies regarding the specific roles of the mitochondrial and the sarcolemmal KATp channels are addressed. (semanticscholar.org)
  • BackgroundMyocardial protection by volatile anesthetics involves activation of cardiac adenosine triphosphate-sensitive potassium (KATP) channels. (semanticscholar.org)
  • Increased expression of adenosine triphosphate-sensitive K+ channels in mitral dysfunction: mechanically stimulated transcription and hypoxia-induced protein stability? (univr.it)
  • The aim of this study was to test whether adenosine triphosphate-sensitive K(+) (KATP) channel expression relates to mechanical and hypoxic stress within the left human heart.The KATP channels play a vital role in preserving the metabolic integrity of the stressed heart. (univr.it)
  • Functional effects of naturally occurring KCNJ11 mutations causing neonatal diabetes on cloned cardiac KATP channels. (ox.ac.uk)
  • Mutations in the pancreatic ATP-sensitive K + (K(ATP)) channel proteins sulfonylurea receptor 1 (SUR1) and Kir6.2, encoded by ABCC8 and KCNJ11, respectively, is the most common cause of the disease. (tcdb.org)
  • SUR2A forms cardiac and smooth muscle-type KATP channels with KCNJ11(Kir6.2) and is involved in regulation and activation. (antibodiesinc.com)
  • Caused in most cases by gain of channel function mutations in the KCNJ11 gene (11p15.1), encoding a subunit of the ATP-sensitive potassium (KATP) channel. (cdc.gov)
  • We used this data, together with estimates of free drug concentrations from binding studies, to predict the extent of sulphonylurea inhibition of KATP channels at therapeutic concentrations in vivo. (ox.ac.uk)
  • 1. Inhibition of cardiomyocyte-specific ATP-sensitive potassium (K ATP ) channels prolongs the action potential during intense ischaemia with attendant antiarrhythmic effects. (elsevier.com)
  • KATP-channel openers namely, cromakalim or pinacidil (10(-7) - 10(-4) M) added cumulatively, elicited a concentration-related inhibition of both amplitude and rate of spontaneous contractions. (who.int)
  • In the absence of Mg2+, both mutations reduced ATP inhibition of SUR1- and SUR2A-containing channels to similar extents, but when Mg2+ was present ATP blocked mutant channels containing SUR1 much less than SUR2A channels. (ox.ac.uk)
  • Conversely, channel opening is potentiated by phosphoinositol bisphosphate (PIP 2 ), which binds to Kir6.2 and reduces channel inhibition by ATP. (tcdb.org)
  • Molecular analysis of the subtype-selective inhibition of cloned K ATP channels by PNU-37883A. (rndsystems.com)
  • Although apamin transiently increased Ca2+ influx into a-cells at low glucose (42.9 +/- 10.6%), sustained SK (38.5 +/- 10.4%) or BK channel inhibition (31.0 +/- 11.7%) decreased alpha-cell Ca2+ influx. (uni-regensburg.de)
  • Total alpha-cell Ca-c(2+) was similarly reduced (28.3 +/- 11.1%) following prolonged treatment with high glucose, but it was not decreased further by SK or BK channel inhibition. (uni-regensburg.de)
  • Sulphonylurea drugs stimulate insulin secretion from pancreatic β-cells primarily by inhibiting ATP sensitive potassium (KATP) channels in the β-cell membrane. (ox.ac.uk)
  • We therefore measured the ability of gliclazide and glibenclamide to inhibit KATP channels and stimulate insulin secretion in the presence of serum albumin. (ox.ac.uk)
  • In contrast, the free gliclazide concentration in plasma is high enough to close KATP channels and stimulate insulin secretion. (ox.ac.uk)
  • K ATP channels mediate insulin secretion in pancreatic islet beta cells, and controlling vascular tone. (chinaphar.com)
  • In pancreatic beta-cells, channels formed by SUR1 and Kir6.2 regulate insulin secretion and are the targets of antidiabetic sulfonylureas. (tcdb.org)
  • This lecture will describe how a membrane protein pore known as the ATP-sensitive potassium (KATP) channel plays a vitally important role in regulating insulin secretion and show how mutations in KATP channel genes can cause neonatal diabetes, a rare genetic form of diabetes that develops soon after birth, and occasionally also developmental problems. (royalsociety.org)
  • Professor Ashcroft's research focuses on ion channels and their role in insulin secretion. (royalsociety.org)
  • She was awarded the Croonian Lecture for outstanding work on the link between glucose metabolism and insulin secretion, and the key role and mechanism of action of the ATP-sensitive potassium channel, and its role in neonatal diabetes. (royalsociety.org)
  • We examined this idea for 3 ADs: paroxetine, clomipramine and, with particular emphasis, fluoxetine, on insulin secretion, mitochondrial function, cellular bioenergetics, KATP channel activity, and caspase activity in murine and human cell-line models of pancreatic β-cells. (nottingham.ac.uk)
  • KCNJ5 gene mutations associated with this condition change single protein building blocks (amino acids) in the potassium channel. (medlineplus.gov)
  • As in aldosterone-producing adenomas (described above), KCNJ5 gene mutations result in production of less-selective potassium channels. (medlineplus.gov)
  • K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. (medlineplus.gov)
  • A Meta-Analysis of Somatic KCNJ5 K(+) Channel Mutations In 1636 Patients With an Aldosterone-Producing Adenoma. (medlineplus.gov)
  • Both mutations also increased resting whole-cell K(ATP) currents through heterozygous SUR1-containing channels to a greater extent than for heterozygous SUR2A-containing channels. (ox.ac.uk)
  • Many mutations in SUR1 render the channel unable to traffic to the cell surface, thereby reducing channel function. (tcdb.org)
  • predominance of recessive KATP channel mutations. (cdc.gov)
  • Investigations into the molecular basis of CHI have led to the discovery of mutations in the sulfonylurea receptor and an inwardly rectifying potassium channel. (medscape.com)
  • Glimepiride block of Kir6.2/SUR1 Kir6.2/SUR2A and Kir6.2/SUR2A and Kir6.2/SUR2B K-ATP channels. (ox.ac.uk)
  • ATP-sensitive K+ (K(ATP)) channels are hetero-octamers of inwardly rectifying K+ channel (Kir6.2) and sulphonylurea receptor subunits (SUR1 in pancreatic beta-cells, SUR2A in heart). (ox.ac.uk)
  • We examined the effects of adenine nucleotides on K(ATP) channels containing wild-type or mutant (Q52R, R201H) Kir6.2 plus either SUR1 or SUR2A. (ox.ac.uk)
  • Kir6.2 is an ATP-sensitive potassium (K ATP ) channel coupling cell metabolism to electrical activity by regulating K + fluxes across the plasma membrane. (tcdb.org)
  • Channel closure is facilitated by ATP, which binds to the pore-forming subunit (Kir6.2). (tcdb.org)
  • a cryo-EM structure of a hamster SUR1/rat Kir6.2 channel bound to a high-affinity sulfonylurea drug glibenclamide and ATP has been solved at 3.63 Å resolution. (tcdb.org)
  • Pharmacological inhibitors and ATP enrich a channel conformation in which the Kir6.2 cytoplasmic domain is closely associated with the transmembrane domain, while depleting one where the Kir6.2 cytoplasmic domain is extended away into the cytoplasm. (tcdb.org)
  • The structures resolved key contacts between the distal N-terminus of Kir6.2 and SUR1's ABC module involving residues implicated in channel function and showed a SUR1 residue, K134, participates in PIP2 binding. (tcdb.org)
  • Proteins and messenger ribonucleic acids (mRNAs) of KATP pore subunits and mRNAs of their known transcriptional regulators (forkhead box [FOX] F2, FOXO1, FOXO3, and hypoxia inducible factor [HIF]-1α) were measured respectively by Western blotting, immunohistochemistry, and quantitative real-time polymerase chain reaction, and submitted to statistical analysis.In all heart chambers, Kir6.2 mRNA correlated with HIF-1α mRNA. (univr.it)
  • Overlapping distribution of K-ATP channel-forming Kir6.2 subunit and the sulfonylurea receptor SUR1 in rodent brain. (mpg.de)
  • Glibenclamide, a KATP-channel blocker inhibited the cromakalim-induced concentration-related relaxation of spontaneous contractions with a significant increase in its mean IC50. (who.int)
  • The present results suggest that in the goat detrusor muscle, agonist and EFS-induced contractile responses were more potently inhibited by cromakalim than pinacidil with activation of glibenclamide sensitive KATP channels. (who.int)
  • Omega-3-polyunsaturated fatty acids (PUFA), which can suppress cardiac myocyte electrical activity, may also reduce ion channel activity in insulin-secreting cells. (cyberleninka.org)
  • The KCNJ5 gene provides instructions for making a protein that functions as a potassium channel, which means that it transports positively charged atoms (ions) of potassium (K + ) into and out of cells. (medlineplus.gov)
  • Redox modulation of vascular tone: focus of potassium channel mechanisms of dilation. (semanticscholar.org)
  • The effect of ROS on potassium channel function in the vasculature is reviewed and discerning the activity of enzymes regulating production or degradation of ROS is important when assessing tissue perfusion in health and disease. (semanticscholar.org)
  • This review highlights the most recent and interesting articles on the physiologic properties and functions of ATP-dependent potassium channels in the cardiovascular system and on the role of the potassium channel openers for the treatment of cardiovascular dysfunction. (semanticscholar.org)
  • AMPA receptors (AMPARs) are glutamate-gated ion channels that mediate the majority of fast excitatory synaptic transmission throughout the brain. (uib.no)
  • KATP currents from mouse pancreatic β-cells and Xenopus oocytes were measured using the patch-clamp technique. (ox.ac.uk)
  • Bovine serum albumin (60g/l) produced a mild, non-significant reduction of gliclazide block of KATP currents in pancreatic β-cells and Xenopus oocytes. (ox.ac.uk)
  • alpha-Cells displayed K-SLOW, currents that were dependent on Ca2+ influx through L- and P/Q-type voltage-dependent Ca2+ channels (VDCCs) as well as Ca2+ released from endoplasmic reticulum stores. (uni-regensburg.de)
  • K ATP channel is a hetero-octameric complex, consisting of four pore-forming Kir6.x and four regulatory sulfonylurea receptor SURx subunits. (chinaphar.com)
  • Expression pattern in brain of TASK-1, TASK-3, and a tandem pore domain K+ channel subunit, TASK-5, associated with the central auditory nervous system. (mpg.de)
  • Kir6.1 is the principal pore-forming subunit of astrocyte but not neuronal plasma membrane K-ATP channels. (mpg.de)
  • These subunits are differentially expressed in various cell types, thus determining the sensitivity of the cells to specific channel modifiers. (chinaphar.com)
  • Ontogeny of gene expression of Kir channel subunits in the rat. (mpg.de)
  • Mg-nucleotide activation of SUR1, but not SUR2A, channels was markedly increased by the R201H mutation. (ox.ac.uk)
  • Four groups of perfused rat hearts were subjected to 36 min of zero-flow ischemia and 44 min of reperfusion with continuous measurements of mechanical function and 31 P NMR high-energy phosphate data: 1) untreated, 2) pinacidil (10 μM) to activate K ATP channels, 3) fasudil (15 μM) to inhibit ROCK, and 4) both fasudil and pinacidil. (elsevier.com)
  • The authors have previously shown that isoflurane enhances sensitivity of the sarcolemmal KATP channel to the opener, pinacidil. (semanticscholar.org)
  • Whereas activation of ATP-dependent potassium (K ATP ) channels greatly improves postischemic myocardial recovery, the final effector mechanism for K ATP channel-induced cardioprotection remains elusive. (elsevier.com)
  • A G-protein-activated inwardly rectifying K+ channel (GIRK4) from human hippocampus associates with other GIRK channels. (mpg.de)
  • It will also reveal how an understanding of KATP channel function has led to a new therapy for patients with neonatal diabetes. (royalsociety.org)
  • Distribution of inwardly rectifying potassium channels in the brain. (mpg.de)
  • Ontogeny of inwardly K + channel expression in the rat. (mpg.de)
  • Distribution and localization of a G protein-coupled inwardly rectifying K+ channel in the rat. (mpg.de)
  • Neither fluoxetine, antimycin nor rotenone could reactivate KATP channel activity blocked by glucose unlike the mitochondrial uncoupler, FCCP. (nottingham.ac.uk)
  • The extracellular glucose concentration monitors the gating of KATP channels of sleep-promoting neurons, highlighting that these neurons can adapt their excitability according to the extracellular energy status… Glucose-induced excitation of sleep-promoting VLPO neurons should therefore be involved in the drowsiness that one feels after a high-sugar meal. (drsharma.ca)
  • Mechanical effects of selective myocyte K ATP channel blockade on basal, β-adrenergic stimulated, and ischemic responses were therefore tested in dogs with cardiac failure induced by tachypacing. (elsevier.com)
  • In this review, we discussed the potential effects of K ATP channel blockers when used under pathological conditions related to diabetics and cerebral ischemic stroke. (chinaphar.com)
  • Cardiomyocyte K ATP channels were inhibited by HMR 1098, and data obtained under basal conditions, during epinephrine infusion to raise metabolic demand, during regional ischaemia, and with combined ischaemia + epinephrine. (elsevier.com)
  • 4. Thus, myocyte-K ATP channels play a negligible role modulating intact in vivo cardiac contraction or arrhythmia in normal and failing heart with and without increased metabolic demand and/or regional ischaemia. (elsevier.com)
  • KATP channels play important roles in controlling and regulating cellular functions in response to metabolic state, which are inhibited by ATP and activated by Mg-ADP, allowing the cell to couple cellular metabolic state (ATP/ADP ratio) to electrical activity of the cell membrane. (chinaphar.com)
  • KATP channels are metabolic sensors that couple cell energetics to membrane excitability. (tcdb.org)
  • The altered potassium channels are less selective, allowing other ions, particularly sodium, to pass through. (medlineplus.gov)
  • IMSEAR at SEARO: Effect of KATP channel openers on myogenic and neurogenic responses in goat urinary bladder. (who.int)
  • Under pathophysiological conditions, K ATP channels play cytoprotective role in cardiac myocytes and neurons during ischemia and/ or hypoxia. (chinaphar.com)
  • Knowlton C, Kutterer S, Roeper J, Canavier CC (2018) Calcium dynamics control K-ATP channel-mediated bursting in substantia nigra dopamine neurons: a combined experimental and modeling study. (yale.edu)
  • RhoA is a GTPase that regulates a variety of cellular processes known to be involved with K ATP channel cardioprotection. (elsevier.com)
  • Mitochondrial KATP channels stabilize intracellular Ca 2+ during hypoxia in retinal horizontal cells of goldfish ( Carassius auratus ) ( Country and Jonz 2021 ). (tcdb.org)
  • Different molecular sites of action for the K ATP channel inhibitors, PNU-99963 and PNU-37883A. (rndsystems.com)
  • a-Cell K s i m ., was decreased by small-conductance Ca'activated K+ (SK) channel inhibitors apamin and UCL 1684. (uni-regensburg.de)
  • She is the Royal Society GlaxoSmithKline Research Professor, a Fellow of Trinity College, Oxford and Director of OXION, a training and research programme on the integrative physiology of ion channels. (hstalks.com)
  • and protein kinasing C- ϵ can modulate the channel function. (semanticscholar.org)
  • Exogenously administered B-type natriuretic peptide (BNP) has been shown to offer cardioprotection through activation of particulate guanylyl cyclase (pGC), protein kinase G (PKG) and KATP channel opening. (uib.no)
  • Brain localization and behavioral impact of the G-protein-gated K + channel subunit GIRK 4. (mpg.de)
  • ATP-sensitive potassium (K ATP ) channels are ubiquitously expressed on the plasma membrane of cells in multiple organs, including the heart, pancreas and brain. (chinaphar.com)
  • Satake, N & Shibata, M 1997, ' The involvement of KCa, KATP and Kv channels in vasorelaxing responses to acetylcholine in rat aortic rings ', Gen Pharmacol , vol. 28, pp. 453-457. (elsevier.com)
  • 2012), ' Heterogeneity of ATP-sensitive K+ channels in cardiac myocytes: enrichment at the intercalated disk. . (antibodiesinc.com)
  • Isoflurane prevents experimental TCM and preserves LV function, an effect not mediated via opening of K-ATP channels. (biomedcentral.com)
  • The syndrome is caused by changes in the structure and function of certain cardiac ion channels and reduced expression of Connexin 43 (Cx43) in the Right Ventricle (RV), predominantly in the Right Ventricular Outflow Tract (VSVD), causing electromechanical abnormalities. (bvsalud.org)
  • Binding of sulphonylureas to plasma proteins - A KATP channel perspective. (ox.ac.uk)
  • The flow of sodium ions into adrenal gland cells affects the electrical charge across the cell membrane, activating another type of channel that allows calcium ions to enter. (medlineplus.gov)
  • These data support the hypothesis that ROCK activity plays a role in K ATP channel-induced cardioprotection. (elsevier.com)
  • Probing the Putative Role of KATP Channels and Biological Variability in a Mathematical Model of Chondrocyte Electrophysiology. (uio.no)
  • What does K-ATP channel do in beta cells when ATP increases within cell? (usmle-forums.com)
  • The effect of isoflurane on vascular KATP channels and compare it with that on cardiac K ATP channels is examined to examine the effect of the drug on vasodilatation in animals and humans. (semanticscholar.org)
  • It seems probable that ATP-sensitive potassium (KATP) channels have a regulatory effect on them. (fip.org)
  • Our goal was to determine whether the activity of a key rhoA effector, rho kinase (ROCK), is required for K ATP channel-induced cardioprotection. (elsevier.com)
  • However, despite the importance of K(ATP) channels in the heart, patients have no obvious cardiac problems. (ox.ac.uk)
  • HN - 2008 MH - Superior Sagittal Sinus UI - D054063 MN - A07.231.908.224.667 MS - The long large endothelium-lined venous channel on the top outer surface of the brain. (bvsalud.org)
  • Potassium channels produced from the KCNJ5 gene are found in several tissues, including the adrenal glands, which are small hormone-producing glands located on top of each kidney. (medlineplus.gov)