KATP Channels
Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.
Potassium Channels, Inwardly Rectifying
Sulfonylurea Receptors
Ion Channels
Potassium Channels
Potassium Channel Blockers
Calcium Channels
Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.
Receptors, Drug
Ion Channel Gating
The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.
Adenosine Triphosphate
Cromakalim
Diazoxide
Pinacidil
ATP-Binding Cassette Transporters
Calcium Channel Blockers
Tolbutamide
Chloride Channels
Patch-Clamp Techniques
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.
Electrophysiology
Potassium Channels, Voltage-Gated
Calcium Channels, L-Type
Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.
Membrane Potentials
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
Potassium Channels, Calcium-Activated
Sarcolemma
Ischemic Preconditioning, Myocardial
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.
Shaker Superfamily of Potassium Channels
Sodium Channel Blockers
Calcium Channels, N-Type
Oocytes
Xenopus laevis
Potassium
An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
TRPC Cation Channels
Large-Conductance Calcium-Activated Potassium Channels
Calcium Channels, T-Type
Cyclic Nucleotide-Gated Cation Channels
Myocardium
Rats, Sprague-Dawley
Nicorandil
Acid Sensing Ion Channels
Epithelial Sodium Channels
Kv1.3 Potassium Channel
Ether-A-Go-Go Potassium Channels
A family of voltage-gated potassium channels that are characterized by long N-terminal and C-terminal intracellular tails. They are named from the Drosophila protein whose mutation causes abnormal leg shaking under ether anesthesia. Their activation kinetics are dependent on extracellular MAGNESIUM and PROTON concentration.
Kv1.2 Potassium Channel
Kv1.1 Potassium Channel
Guanidines
Adenosine Diphosphate
TRPM Cation Channels
Xenopus
Kv1.5 Potassium Channel
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Dose-Response Relationship, Drug
Calcium Channel Agonists
Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.
TRPV Cation Channels
Congenital Hyperinsulinism
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).
Islets of Langerhans
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.
Cells, Cultured
KCNQ Potassium Channels
Calcium
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Shab Potassium Channels
Guinea Pigs
Action Potentials
Cell Membrane
Rats, Wistar
Mutation
Small-Conductance Calcium-Activated Potassium Channels
Protein Subunits
Kv1.4 Potassium Channel
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Amino Acid Sequence
Transient Receptor Potential Channels
A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN repeats are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES.
Dihydropyridines
Shaw Potassium Channels
Myocytes, Cardiac
Minoxidil
Neurons
Shal Potassium Channels
Thiamylal
Vasodilation
Sodium
Rabbits
Rana esculenta
Magnesium
Protein Structure, Tertiary
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Anti-Arrhythmia Agents
Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.
KCNQ2 Potassium Channel
Heart Ventricles
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Calcium Channels, P-Type
COS Cells
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
Receptors, Purinergic P1
NAV1.5 Voltage-Gated Sodium Channel
Adenosine
Myocardial Ischemia
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).
Ryanodine Receptor Calcium Release Channel
A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.
KCNQ3 Potassium Channel
Barium
RNA, Complementary
Intermediate-Conductance Calcium-Activated Potassium Channels
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
Insulinoma
Models, Biological
Scorpion Venoms
Transfection
NAV1.2 Voltage-Gated Sodium Channel
A voltage-gated sodium channel subtype that mediates the sodium ion permeability of excitable membranes. Defects in the SCN2A gene which codes for the alpha subunit of this sodium channel are associated with benign familial infantile seizures type 3, and early infantile epileptic encephalopathy type 11.
Myocardial Reperfusion Injury
Delayed Rectifier Potassium Channels
Insulin
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).
Calcium Channels, R-Type
Ischemic Preconditioning
Binding Sites
2,4-Dinitrophenol
Models, Molecular
Charybdotoxin
Ion Transport
Glucose
Cricetinae
Membrane Proteins
Nucleotides
Anesthetics, Inhalation
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)
Voltage-Gated Sodium Channels
Enzyme Inhibitors
Sodium Cyanide
8,11,14-Eicosatrienoic Acid
Hydrogen-Ion Concentration
Rubidium Radioisotopes
Sodium Azide
Cyclic AMP-Dependent Protein Kinases
Voltage-Dependent Anion Channels
Cyclic GMP
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)
Lipid Bilayers
Dogs
Insulin-Secreting Cells
Protein Kinase C
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
Nifedipine
Membrane Transport Modulators
Cations
Benzophenanthridines
Isoflurane
Nitric Oxide
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.
NAV1.4 Voltage-Gated Sodium Channel
Nitroprusside
Pyridines
Signal Transduction
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Muscle, Skeletal
Hydrogen Sulfide
Tetrodotoxin
Calcium Gluconate
HEK293 Cells
Gramicidin
Degenerin Sodium Channels
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.
Pia Mater
Mutagenesis, Site-Directed
Sodium Channel Agonists
Cloning, Molecular
Mice, Knockout
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.
4-Aminopyridine
Protein Binding
Apamin
omega-Conotoxin GVIA
RNA, Messenger
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Cyclic AMP
Mesenteric Arteries
Protein Conformation
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Ions
Syntaxin 1
Cardiotonic Agents
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)
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Substrate Control of Insulin Release - Comprehensive Physiology
A Kir6.2 Mutation Causing Neonatal Diabetes Impairs Electrical Activity and Insulin Secretion From INS-1 β-Cells | Diabetes
生命科学-官方网站
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The KATP channel activator diazoxide ameliorates amyloid-β and Tau pathologies and improves memory in the 3xTgAD mouse model of...
The ATP-Sensitive Potassium Channel Subunit, Kir6.1, in Vascular Smooth Muscle Plays a Major Role in Blood Pressure Control |...
Advances in cardiac ATP-Sensitive K <sup>+</sup> channelopathies from molecules to...
Coronary spasm and acute myocardial infarction due to a mutation (V734I) in the nucleotide binding domain 1 of ABCC9. - Oxford...
Octameric Stoichiometry of the KATP Channel Complex | JGP
Zinc is both an intracellular and extracellular regulator of KATP channel function
Potassium Channel Function in Vascular Disease | Arteriosclerosis, Thrombosis, and Vascular Biology
Potassium Channel Function in Vascular Disease | Arteriosclerosis, Thrombosis, and Vascular Biology
Plus it
Hypertrophy decreases cardiac KATP channel responsiveness to exogenous and locally generated (glycolytic) ATP.
Plus it
Interaction of the Cytosolic Domains of the Kir6.2 Subunit of the KATP Channel Is Modulated by Sulfonylureas | Diabetes
Alchemy in the Soup: Transforming Metabolic Signals to Excitability | Science Signaling
Endothelial biology and ATP-sensitive potassium channels.
Regulation of Subsarcolemmal ATP by Subsarcolemmal KATP Channels: Is it Important for Cardioprotection - Discovery - the...
Short-term effects of glipizide (an adenosine triphosphate-sensitive potassium channel inhibitor) on cardiopulmonary...
Functional effects of naturally occurring KCNJ11 mutations causing neonatal diabetes on cloned cardiac KATP channels. - Oxford...
Spontaneous contractions of the pig urinary bladder: The effect of ATP-sensitive potassium channels and the role of the mucosa<...
Abstract 16645: Abcc9 Contributes to Mitochondrial Katp Function and Protection From Cardiomyopathy | Circulation
Glucose-dependent regulation of rhythmic action potential firing in pancreatic beta-cells by K(ATP)-channel modulation. -...
Hydrochlorothiazide: An hyperglycaemia-inducing agent and K-ATP channel agonist in human beta-cells and clonal insulin...
Autocrine insulin increases plasma membrane K<sub>ATP</sub> channel via PI3K-VAMP2 pathway in MIN6...
Context: ATP-sensitive potassium (KATP) stations regulate insulin secretion by coupling glucose | Role of NK1 and NK2 receptors...
Renaud, Jean-Marc | Département de médecine cellulaire et moléculaire | Université dOttawa
Mechanisms by which glucose can control insulin release independently from its action on adenosine triphosphate-sensitive K+...
Fiziologichnyi Zhurnal
CiNii 論文 - 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
Beneficial Effect of Propofol on Arterial Adenosine Triphosphate-sensitive K+Channel Function Impaired by Thromboxane |...
JCI -
The ATP-sensitive K+ channel mediates hypotension in endotoxemia and hypoxic lactic acidosis in dog.
Impact of In Vivo
Preconditioning by Isoflurane on Adenosine Triphosphate-sensitive Potassium Channels in the Rat Heart...
Cerebral ATP-Sensitive Potassium Channels During Acute Reduction of Carotid Blood Flow | Hypertension
AMP-activated protein kinase connects cellular energy metabolism to KATP channel function. | Harvard Catalyst Profiles |...
PSD95 scaffolding of vascular K+ channels in hypertension - Sung Rhee
Differences in the mechanism of metabolic regulation of ATP-se...
From My Kitchen With Love: Petola Ular Goreng
List of causes of hypoglycemia
H. Huopio1, S.-L. Shyng, T. Otonkoski3, and C. G. Nichols4 (2002-08-01). "KATP channels and insulin secretion disorders". ...
Bimakalim
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). ...
ATP-sensitive potassium channel
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 ...
Cantú syndrome
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 ...
Colin Nichols
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 ...
Sulfonylurea receptor
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 ...
HMR 1883
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): ...
ABCC9
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. ...
Imidazoline receptor
It may be associated with ATP-sensitive K+ (KATP) channels. AGN 192403Moxonidine CR-4056 Phenyzoline (2-(2-phenylethyl)-4,5- ...
KCNJ5
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: ...
Kir6.2
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 ...
Caveolin 3
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. ...
Congenital hyperinsulinism
... 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 ...
Verrucotoxin
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). ...
ENSA (gene)
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 ...
BacMam
"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; ...
Capric acid
"Ketogenic Diet Metabolites Reduce Firing in Central Neurons by Opening KATP Channels". The Journal of Neuroscience. 27 (14): ...
Maturity-onset diabetes of the young
Sulfonylureas are effective in the KATP channel forms of neonatal-onset diabetes. The mouse model of MODY diabetes suggested ...
NeuroAiD
MLC901 can activate KATP channels, which has a neuroprotective effect against brain ischemia. Neuroaid is not effective in ...
KCNJ8
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 ...
KATP
... 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 - ...
Glutamate dehydrogenase 1
"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 ...
BW373U86
Gross ER, Hsu AK, Gross GJ (July 2007). "GSK3β inhibition and KATP channel opening mediate acute opioid-induced ...
Hyperinsulinism-hyperammonemia syndrome
"Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel ...
Frances Ashcroft
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 ...
Al Aynsley-Green
"Loss of functional KATP channels in pancreatic β-cells causes persistent hyperinsulinemic hypoglycemia of infancy". Nature ...
Benign early repolarization
"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 ...
Neonatal diabetes
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 ...
ARPP-19
... a possible regulator of sulfonylurea-sensitive KATP channel: molecular cloning, expression and biological properties". Proc. ...
Diabetes medication
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. ...
KCNJ6
"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 ...
Pyruvate cycling
June 2008). "Elimination of KATP Channels in Mouse Islets Results in Elevated U-13CGlucose Metabolism, Glutaminolysis, and ...
Ion channel
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-FM
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, ...
Beta cell
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 ...
Akinori Noma
... 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 ...
Glibenclamide
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 ...
Meglitinide
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 ...
Pike-Pawnee Village Site
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 ...
Jennifer S. Lawton
"Exploitation of the KATP Channel Opener Diazoxide during Cardiac Surgery." During her tenure at the Washington University ...
Periodic paralysis
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... ...
Nicorandil
... 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 ...
Permanent neonatal diabetes
... which codes for the Kir6.2 subunit of the beta cell KATP channel. This disease is considered to be a type of maturity onset ...
Hyperinsulinemic hypoglycemia
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 ...
Vagus nerve
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 ...
Mitiglinide
... is thought to stimulate insulin secretion by closing the ATP-sensitive potassium KATP channels in pancreatic β ...
Mannoheptulose
... therefore no increase in ATP concentration which is required to close the KATP channel in the beta cells of the pancreas ...
Binding of sulphonylureas to plasma proteins - A KATP channel perspective. - Oxford Neuroscience
... 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 ...
Effects of cardioselective K<sub>ATP</sub> channel antagonism on basal, stimulated, and ischaemic myocardial function in in...
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 ...
What does K-ATP channel do in beta cells when ATP increases within cell? | USMLE Forums
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. - Department of Physiology,...
Fasudil prevents K<sub>ATP</sub> channel-induced improvement in postischemic functional...
... 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 ...
KCNJ5 gene: MedlinePlus Genetics
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 ...
IMSEAR at SEARO: Effect of KATP channel openers on myogenic and neurogenic responses in goat urinary bladder.
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 - SZETO - Acta Pharmacologica Sinica
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- ...
Functional effects of naturally occurring KCNJ11 mutations causing neonatal diabetes on cloned cardiac KATP channels. - Oxford...
... 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 Prodrug
PDF] Contribution of Reactive Oxygen Species to Isoflurane-induced Sensitization of Cardiac Sarcolemmal Adenosine Triphosphate...
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 ...
DeCS 2010 - February 12, 2010 version
The involvement of KCa, KATP and Kv channels in vasorelaxing responses to acetylcholine in rat aortic rings<...
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 ...
Science Clips - Monday, April 25, 2011
Sulfide regulation of cardiovascular function in health and disease | Nature Reviews Cardiology
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. ...
Publications | OHSU
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 ...
TCDB » SEARCH
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 ...
PNU 37883 hydrochloride (CAS 57568-80-6): R&D Systems
Description: Vascular Kir6 (KATP) channel blocker Chemical Name: N-Cyclohexyl-N-tricyclo[3.3.1.13,7]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 ...
Abstracts - FIP - International Pharmaceutical Federation
Search results - ORA - Oxford University Research Archive
Prof. Frances Mary Ashcroft | HSTalks
Glucagon-Like Peptide-1 and Its Implications in Obesity | IntechOpen
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% ...
Croonian Lecture | Royal Society
... 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 ...
Risk Factors Contributing to Type 2 Diabetes and Recent Advances in the Treatment and Prevention
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 ...
Andre Terzic - Research output - Mayo Clinic
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, ...
Glucose-mediated inhibition of calcium-activated potassium channels limits α-cell calcium influx and glucagon secretion -...
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+ ( ...
Maria Perona Fjeldstad - Department of Informatics
The AMEDEO Literature Guide
Research Areas - Products
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 ...
Sarcolemmal KATp channelsAdenosine triphosphate-sensitiveKCNJ11InhibitionSecretionMutationsKir6.2GlibenclamideInsulinPotassium channelSynaptic transmissionCurrentsPoreSubunitsSUR1PinacidilMyocardialGIRK4Neonatal diabetesInwardlyGlucoseIschemicMetabolicSelectiveOpenersNeuronsCellular2021InhibitorsPhysiologyProteinPlasma membraneResponsesCardiac myocytesFunctionProteinsCalciumRoleBeta cellsEffectActivityHeartBrainGene
Sarcolemmal KATp channels1
- 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)
Adenosine triphosphate-sensitive3
- 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)
KCNJ114
- 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)
Inhibition8
- 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)
Secretion9
- 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)
Mutations8
- 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)
Kir6.210
- 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)
Glibenclamide2
- 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)
Insulin1
- 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)
Potassium channel4
- 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)
Synaptic transmission1
- AMPA receptors (AMPARs) are glutamate-gated ion channels that mediate the majority of fast excitatory synaptic transmission throughout the brain. (uib.no)
Currents3
- 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)
Pore3
- 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)
Subunits2
- 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)
SUR11
- Mg-nucleotide activation of SUR1, but not SUR2A, channels was markedly increased by the R201H mutation. (ox.ac.uk)
Pinacidil2
- 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)
Myocardial1
- 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)
GIRK41
- A G-protein-activated inwardly rectifying K+ channel (GIRK4) from human hippocampus associates with other GIRK channels. (mpg.de)
Neonatal diabetes1
- It will also reveal how an understanding of KATP channel function has led to a new therapy for patients with neonatal diabetes. (royalsociety.org)
Inwardly3
Glucose2
- 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)
Ischemic2
- 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)
Metabolic4
- 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)
Selective1
- The altered potassium channels are less selective, allowing other ions, particularly sodium, to pass through. (medlineplus.gov)
Openers1
- IMSEAR at SEARO: Effect of KATP channel openers on myogenic and neurogenic responses in goat urinary bladder. (who.int)
Neurons2
- 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)
Cellular1
- RhoA is a GTPase that regulates a variety of cellular processes known to be involved with K ATP channel cardioprotection. (elsevier.com)
20211
- Mitochondrial KATP channels stabilize intracellular Ca 2+ during hypoxia in retinal horizontal cells of goldfish ( Carassius auratus ) ( Country and Jonz 2021 ). (tcdb.org)
Inhibitors2
- 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)
Physiology1
- 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)
Protein3
- 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)
Plasma membrane1
- 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)
Responses1
- 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)
Cardiac myocytes1
- 2012), ' Heterogeneity of ATP-sensitive K+ channels in cardiac myocytes: enrichment at the intercalated disk. . (antibodiesinc.com)
Function2
- 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)
Proteins1
- Binding of sulphonylureas to plasma proteins - A KATP channel perspective. (ox.ac.uk)
Calcium1
- 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)
Role2
- 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)
Beta cells1
- What does K-ATP channel do in beta cells when ATP increases within cell? (usmle-forums.com)
Effect2
- 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)
Activity1
- 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)
Heart1
- However, despite the importance of K(ATP) channels in the heart, patients have no obvious cardiac problems. (ox.ac.uk)
Brain1
- 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)
Gene1
- 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)