Potassium Channels: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.Potassium: An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.Potassium Channels, Inwardly Rectifying: Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.Potassium Channel Blockers: A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.Potassium Channels, Voltage-Gated: Potassium channel whose permeability to ions is extremely sensitive to the transmembrane potential difference. The opening of these channels is induced by the membrane depolarization of the ACTION POTENTIAL.Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.Shaker Superfamily of Potassium Channels: Voltage-gated potassium channels whose primary subunits contain six transmembrane segments and form tetramers to create a pore with a voltage sensor. They are related to their founding member, shaker protein, Drosophila.Kv1.3 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.Ion Channel Gating: The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.Kv1.2 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.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.Kv1.1 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.Potassium Channels, Calcium-Activated: Potassium channels whose activation is dependent on intracellular calcium concentrations.Ether-A-Go-Go Potassium Channels: A family of voltage-gated potassium channels that are characterized by long N-terminal and C-terminal intracellular tails. They are named from the Drosophila protein whose mutation causes abnormal leg shaking under ether anesthesia. Their activation kinetics are dependent on extracellular MAGNESIUM and PROTON concentration.Shaw Potassium Channels: A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.KCNQ1 Potassium Channel: A voltage-gated potassium channel that is expressed primarily in the HEART.KCNQ Potassium Channels: A family of delayed rectifier voltage-gated potassium channels that share homology with their founding member, KCNQ1 PROTEIN. KCNQ potassium channels have been implicated in a variety of diseases including LONG QT SYNDROME; DEAFNESS; and EPILEPSY.Kv1.5 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that conducts a delayed rectifier current. It contributes to ACTION POTENTIAL repolarization of MYOCYTES in HEART ATRIA.Kv1.4 Potassium Channel: A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.Shab Potassium Channels: A subfamily of shaker potassium channels that shares homology with its founding member, Shab protein, Drosophila. They regulate delayed rectifier currents in the NERVOUS SYSTEM of DROSOPHILA and in the SKELETAL MUSCLE and HEART of VERTEBRATES.Large-Conductance Calcium-Activated Potassium Channels: A major class of calcium activated potassium channels whose members are voltage-dependent. MaxiK channels are activated by either membrane depolarization or an increase in intracellular Ca(2+). They are key regulators of calcium and electrical signaling in a variety of tissues.KATP Channels: Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.KCNQ2 Potassium Channel: A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.Potassium Channels, Tandem Pore Domain: Potassium channels that contain two pores in tandem. They are responsible for baseline or leak currents and may be the most numerous of all K channels.KCNQ3 Potassium Channel: A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is closely related to KCNQ2 POTASSIUM CHANNEL. It is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.G Protein-Coupled Inwardly-Rectifying Potassium Channels: A family of inwardly-rectifying potassium channels that are activated by PERTUSSIS TOXIN sensitive G-PROTEIN-COUPLED RECEPTORS. GIRK potassium channels are primarily activated by the complex of GTP-BINDING PROTEIN BETA SUBUNITS and GTP-BINDING PROTEIN GAMMA SUBUNITS.Shal Potassium Channels: A shaker subfamily of potassium channels that participate in transient outward potassium currents by activating at subthreshold MEMBRANE POTENTIALS, inactivating rapidly, and recovering from inactivation quickly.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.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.Small-Conductance Calcium-Activated Potassium Channels: A major class of calcium-activated potassium channels that are found primarily in excitable CELLS. They play important roles in the transmission of ACTION POTENTIALS and generate a long-lasting hyperpolarization known as the slow afterhyperpolarization.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.Chloride Channels: Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.Delayed Rectifier Potassium Channels: A group of slow opening and closing voltage-gated potassium channels. Because of their delayed activation kinetics they play an important role in controlling ACTION POTENTIAL duration.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.Tetraethylammonium: A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.Oocytes: Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).Xenopus laevis: The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.Calcium Channels, L-Type: Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.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: 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.Intermediate-Conductance Calcium-Activated Potassium Channels: A major class of calcium-activated potassium channels that were originally discovered in ERYTHROCYTES. They are found primarily in non-excitable CELLS and set up electrical gradients for PASSIVE ION TRANSPORT.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Heterotrimeric GTP-Binding Proteins: GTP-BINDING PROTEINS that contain three non-identical subunits. They are found associated with members of the seven transmembrane domain superfamily of G-PROTEIN-COUPLED RECEPTORS. Upon activation the GTP-BINDING PROTEIN ALPHA SUBUNIT of the complex dissociates leaving a dimer of a GTP-BINDING PROTEIN BETA SUBUNIT bound to a GTP-BINDING PROTEIN GAMMA SUBUNIT.4-Aminopyridine: One of the POTASSIUM CHANNEL BLOCKERS, with secondary effect on calcium currents, which is used mainly as a research tool and to characterize channel subtypes.Large-Conductance Calcium-Activated Potassium Channel alpha Subunits: The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.Scorpion Venoms: Venoms from animals of the order Scorpionida of the class Arachnida. They contain neuro- and hemotoxins, enzymes, and various other factors that may release acetylcholine and catecholamines from nerve endings. Of the several protein toxins that have been characterized, most are immunogenic.Cromakalim: A potassium-channel opening vasodilator that has been investigated in the management of hypertension. It has also been tried in patients with asthma. (Martindale, The Extra Pharmacopoeia, 30th ed, p352)Pinacidil: A guanidine that opens POTASSIUM CHANNELS producing direct peripheral vasodilatation of the ARTERIOLES. It reduces BLOOD PRESSURE and peripheral resistance and produces fluid retention. (Martindale The Extra Pharmacopoeia, 31st ed)Kinetics: The rate dynamics in chemical or physical systems.Charybdotoxin: A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.Potassium, Dietary: Potassium or potassium compounds used in foods or as foods.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.Sodium Channel Blockers: A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.Calcium Channels, N-Type: CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.Sulfonylurea Receptors: ATP-BINDING CASSETTE PROTEINS that are highly conserved and widely expressed in nature. They form an integral part of the ATP-sensitive potassium channel complex which has two intracellular nucleotide folds that bind to sulfonylureas and their analogs.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous.Tetraethylammonium CompoundsCell Line: Established cell cultures that have the potential to propagate indefinitely.Barium Compounds: Inorganic compounds that contain barium as an integral part of the molecule.Potassium Deficiency: A condition due to decreased dietary intake of potassium, as in starvation or failure to administer in intravenous solutions, or to gastrointestinal loss in diarrhea, chronic laxative abuse, vomiting, gastric suction, or bowel diversion. Severe potassium deficiency may produce muscular weakness and lead to paralysis and respiratory failure. Muscular malfunction may result in hypoventilation, paralytic ileus, hypotension, muscle twitches, tetany, and rhabomyolysis. Nephropathy from potassium deficit impairs the concentrating mechanism, producing POLYURIA and decreased maximal urinary concentrating ability with secondary POLYDIPSIA. (Merck Manual, 16th ed)Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.RGS Proteins: A large family of evolutionarily conserved proteins that function as negative regulators of HETEROTRIMERIC GTP-BINDING PROTEINS. RGS PROTEINS act by increasing the GTPase activity of the G alpha subunit of a heterotrimeric GTP-binding protein, causing it to revert to its inactive (GDP-bound) form.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.GTP-Binding Protein beta Subunits: Heterotrimeric GTP-binding protein subunits that tightly associate with GTP-BINDING PROTEIN GAMMA SUBUNITS. A dimer of beta and gamma subunits is formed when the GTP-BINDING PROTEIN ALPHA SUBUNIT dissociates from the GTP-binding protein heterotrimeric complex. The beta-gamma dimer can play an important role in signal transduction by interacting with a variety of second messengers.TRPC Cation Channels: A subgroup of TRP cation channels that contain 3-4 ANKYRIN REPEAT DOMAINS and a conserved C-terminal domain. Members are highly expressed in the CENTRAL NERVOUS SYSTEM. Selectivity for calcium over sodium ranges from 0.5 to 10.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Potassium Compounds: Inorganic compounds that contain potassium as an integral part of the molecule.Cyclic Nucleotide-Gated Cation Channels: A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore-loop cation channels. They are expressed in OLFACTORY NERVE cilia and in PHOTORECEPTOR CELLS and some PLANTS.Calcium Channels, T-Type: A heterogenous group of transient or low voltage activated type CALCIUM CHANNELS. They are found in cardiac myocyte membranes, the sinoatrial node, Purkinje cells of the heart and the central nervous system.Protein Subunits: Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.Benzopyrans: Compounds with a core of fused benzo-pyran rings.Apamin: A highly neurotoxic polypeptide from the venom of the honey bee (Apis mellifera). It consists of 18 amino acids with two disulfide bridges and causes hyperexcitability resulting in convulsions and respiratory paralysis.Receptors, Drug: Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.Large-Conductance Calcium-Activated Potassium Channel beta Subunits: The regulatory subunits of large-conductance calcium-activated potassium channels.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.GTP-Binding Protein alpha Subunits: The GTPase-containing subunits of heterotrimeric GTP-binding proteins. When dissociated from the heterotrimeric complex these subunits interact with a variety of second messenger systems. Hydrolysis of GTP by the inherent GTPase activity of the subunit causes it to revert to its inactive (heterotrimeric) form. The GTP-Binding protein alpha subunits are grouped into families according to the type of action they have on second messenger systems.Guanosine 5'-O-(3-Thiotriphosphate): Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Potassium Chloride: A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.GTP-Binding Protein gamma Subunits: Heterotrimeric GTP-binding protein subunits that tightly associate with GTP-BINDING PROTEIN BETA SUBUNITS. A dimer of beta and gamma subunits is formed when the GTP-BINDING PROTEIN ALPHA SUBUNIT dissociates from the GTP-binding protein heterotrimeric complex. The beta-gamma dimer can play an important role in signal transduction by interacting with a variety of second messengers.Nicorandil: A derivative of the NIACINAMIDE that is structurally combined with an organic nitrate. It is a potassium-channel opener that causes vasodilatation of arterioles and large coronary arteries. Its nitrate-like properties produce venous vasodilation through stimulation of guanylate cyclase.Cesium: A member of the alkali metals. It has an atomic symbol Cs, atomic number 50, and atomic weight 132.91. Cesium has many industrial applications, including the construction of atomic clocks based on its atomic vibrational frequency.Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active, passive or facilitated. Ions may travel by themselves (uniport), or as a group of two or more ions in the same (symport) or opposite (antiport) directions.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.GTP-Binding Protein alpha Subunits, Gi-Go: A family of heterotrimeric GTP-binding protein alpha subunits that were originally identified by their ability to inhibit ADENYLYL CYCLASES. Members of this family can couple to beta and gamma G-protein subunits that activate POTASSIUM CHANNELS. The Gi-Go part of the name is also spelled Gi/Go.Acid Sensing Ion Channels: A family of proton-gated sodium channels that are primarily expressed in neuronal tissue. They are AMILORIDE-sensitive and are implicated in the signaling of a variety of neurological stimuli, most notably that of pain in response to acidic conditions.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Epithelial Sodium Channels: Sodium channels found on salt-reabsorbing EPITHELIAL CELLS that line the distal NEPHRON; the distal COLON; SALIVARY DUCTS; SWEAT GLANDS; and the LUNG. They are AMILORIDE-sensitive and play a critical role in the control of sodium balance, BLOOD VOLUME, and BLOOD PRESSURE.Diazoxide: A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Pertussis Toxin: One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.Elapid Venoms: Venoms from snakes of the family Elapidae, including cobras, kraits, mambas, coral, tiger, and Australian snakes. The venoms contain polypeptide toxins of various kinds, cytolytic, hemolytic, and neurotoxic factors, but fewer enzymes than viper or crotalid venoms. Many of the toxins have been characterized.Potassium Isotopes: Stable potassium atoms that have the same atomic number as the element potassium, but differ in atomic weight. K-41 is a stable potassium isotope.TRPV Cation Channels: A subgroup of TRP cation channels named after vanilloid receptor. They are very sensitive to TEMPERATURE and hot spicy food and CAPSAICIN. They have the TRP domain and ANKYRIN repeats. Selectivity for CALCIUM over SODIUM ranges from 3 to 100 fold.Decanoic Acids: 10-carbon saturated monocarboxylic acids.TRPM Cation Channels: A subgroup of TRP cation channels named after melastatin protein. They have the TRP domain but lack ANKYRIN repeats. Enzyme domains in the C-terminus leads to them being called chanzymes.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Hydroxy Acids: Organic compounds containing both the hydroxyl and carboxyl radicals.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Kv1.6 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that has been described in NEURONS and ASTROCYTES.Virulence Factors, Bordetella: A set of BACTERIAL ADHESINS and TOXINS, BIOLOGICAL produced by BORDETELLA organisms that determine the pathogenesis of BORDETELLA INFECTIONS, such as WHOOPING COUGH. They include filamentous hemagglutinin; FIMBRIAE PROTEINS; pertactin; PERTUSSIS TOXIN; ADENYLATE CYCLASE TOXIN; dermonecrotic toxin; tracheal cytotoxin; Bordetella LIPOPOLYSACCHARIDES; and tracheal colonization factor.Rubidium: An element that is an alkali metal. It has an atomic symbol Rb, atomic number 37, and atomic weight 85.47. It is used as a chemical reagent and in the manufacture of photoelectric cells.Potassium Radioisotopes: Unstable isotopes of potassium that decay or disintegrate emitting radiation. K atoms with atomic weights 37, 38, 40, and 42-45 are radioactive potassium isotopes.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).Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Chlorides: Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.PhenylenediaminesGTP-Binding Protein alpha Subunits, Gq-G11: A family of heterotrimeric GTP-binding protein alpha subunits that activate TYPE C PHOSPHOLIPASES dependent signaling pathways. The Gq-G11 part of the name is also spelled Gq/G11.Kv Channel-Interacting Proteins: A family of neuronal calcium-sensor proteins that interact with and regulate potassium channels, type A.Scorpions: Arthropods of the order Scorpiones, of which 1500 to 2000 species have been described. The most common live in tropical or subtropical areas. They are nocturnal and feed principally on insects and other arthropods. They are large arachnids but do not attack man spontaneously. They have a venomous sting. Their medical significance varies considerably and is dependent on their habits and venom potency rather than on their size. At most, the sting is equivalent to that of a hornet but certain species possess a highly toxic venom potentially fatal to humans. (From Dorland, 27th ed; Smith, Insects and Other Arthropods of Medical Importance, 1973, p417; Barnes, Invertebrate Zoology, 5th ed, p503)Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Streptomyces lividans: An actinomycete used for production of commercial ANTIBIOTICS and as a host for gene cloning.Long QT Syndrome: A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.Aminopyridines: Pyridines substituted in any position with an amino group. May be hydrogenated, but must retain at least one double bond.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.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).)Electric Stimulation: Use of electric potential or currents to elicit biological responses.Calcium Channels, P-Type: CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.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.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Picolines: A group of compounds that are monomethyl derivatives of pyridines. (From Dorland, 28th ed)Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as CATIONS; those with a negative charge are ANIONS.Minoxidil: A potent direct-acting peripheral vasodilator (VASODILATOR AGENTS) that reduces peripheral resistance and produces a fall in BLOOD PRESSURE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p371)Cation Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of positively charged molecules (cations) across a biological membrane.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Tetrodotoxin: An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.Cricetulus: A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.Decapodiformes: A superorder of CEPHALOPODS comprised of squid, cuttlefish, and their relatives. Their distinguishing feature is the modification of their fourth pair of arms into tentacles, resulting in 10 limbs.Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: A subgroup of cyclic nucleotide-regulated ION CHANNELS of the superfamily of pore-loop cation channels that are opened by hyperpolarization rather than depolarization. The ion conducting pore passes SODIUM, CALCIUM, and POTASSIUM cations with a preference for potassium.Cations: Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.Heart: The hollow, muscular organ that maintains the circulation of the blood.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.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.Hypokalemia: Abnormally low potassium concentration in the blood. It may result from potassium loss by renal secretion or by the gastrointestinal route, as by vomiting or diarrhea. It may be manifested clinically by neuromuscular disorders ranging from weakness to paralysis, by electrocardiographic abnormalities (depression of the T wave and elevation of the U wave), by renal disease, and by gastrointestinal disorders. (Dorland, 27th ed)Calcium Channels, Q-Type: CALCIUM CHANNELS located in the neurons of the brain.RNA, Complementary: Synthetic transcripts of a specific DNA molecule or fragment, made by an in vitro transcription system. This cRNA can be labeled with radioactive uracil and then used as a probe. (King & Stansfield, A Dictionary of Genetics, 4th ed)Potassium Iodide: An inorganic compound that is used as a source of iodine in thyrotoxic crisis and in the preparation of thyrotoxic patients for thyroidectomy. (From Dorland, 27th ed)Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.Biophysics: The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.Quinidine: An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.NAV1.5 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of CARDIOMYOCYTES. Defects in the SCN5A gene, which codes for the alpha subunit of this sodium channel, are associated with a variety of CARDIAC DISEASES that result from loss of sodium channel function.Receptors, Muscarinic: One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.Quaternary Ammonium Compounds: Derivatives of ammonium compounds, NH4+ Y-, in which all four of the hydrogens bonded to nitrogen have been replaced with hydrocarbyl groups. These are distinguished from IMINES which are RN=CR2.GTP-Binding Protein alpha Subunits, Gs: A family of heterotrimeric GTP-binding protein alpha subunits that activate ADENYLYL CYCLASES.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.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Tolbutamide: A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Cnidarian Venoms: Venoms from jellyfish; CORALS; SEA ANEMONES; etc. They contain hemo-, cardio-, dermo- , and neuro-toxic substances and probably ENZYMES. They include palytoxin, sarcophine, and anthopleurine.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.GTP-Binding Protein alpha Subunit, Gi2: A PERTUSSIS TOXIN-sensitive GTP-binding protein alpha subunit. It couples with a variety of CELL SURFACE RECEPTORS, has been implicated in INTERLEUKIN-12 production, and may play a role in INFLAMMATORY BOWEL DISEASES.Guanosine Diphosphate: A guanine nucleotide containing two phosphate groups esterified to the sugar moiety.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Rubidium Radioisotopes: Unstable isotopes of rubidium that decay or disintegrate emitting radiation. Rb atoms with atomic weights 79-84, and 86-95 are radioactive rubidium isotopes.Ryanodine Receptor Calcium Release Channel: A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Biophysical Phenomena: The physical characteristics and processes of biological systems.Cations, Monovalent: Positively charged atoms, radicals or group of atoms with a valence of plus 1, which travel to the cathode or negative pole during electrolysis.Nerve Tissue ProteinsDNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Acetylcholine: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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.Myocytes, Cardiac: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.

Somatostatin induces hyperpolarization in pancreatic islet alpha cells by activating a G protein-gated K+ channel. (1/480)

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

Selective activation of heterologously expressed G protein-gated K+ channels by M2 muscarinic receptors in rat sympathetic neurones. (2/480)

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

Identification of a GABAB receptor subunit, gb2, required for functional GABAB receptor activity. (3/480)

G protein-coupled receptors are commonly thought to bind their cognate ligands and elicit functional responses primarily as monomeric receptors. In studying the recombinant gamma-aminobutyric acid, type B (GABAB) receptor (gb1a) and a GABAB-like orphan receptor (gb2), we observed that both receptors are functionally inactive when expressed individually in multiple heterologous systems. Characterization of the tissue distribution of each of the receptors by in situ hybridization histochemistry in rat brain revealed co-localization of gb1 and gb2 transcripts in many brain regions, suggesting the hypothesis that gb1 and gb2 may interact in vivo. In three established functional systems (inwardly rectifying K+ channel currents in Xenopus oocytes, melanophore pigment aggregation, and direct cAMP measurements in HEK-293 cells), GABA mediated a functional response in cells coexpressing gb1a and gb2 but not in cells expressing either receptor individually. This GABA activity could be blocked with the GABAB receptor antagonist CGP71872. In COS-7 cells coexpressing gb1a and gb2 receptors, co-immunoprecipitation of gb1a and gb2 receptors was demonstrated, indicating that gb1a and gb2 act as subunits in the formation of a functional GABAB receptor.  (+info)

Secretagogue-induced exocytosis recruits G protein-gated K+ channels to plasma membrane in endocrine cells. (4/480)

Stimulation-regulated fusion of vesicles to the plasma membrane is an essential step for hormone secretion but may also serve for the recruitment of functional proteins to the plasma membrane. While studying the distribution of G protein-gated K+ (KG) channels in the anterior pituitary lobe, we found KG channel subunits Kir3.1 and Kir3.4 localized on the membranes of intracellular dense core vesicles that contained thyrotropin. Stimulation of these thyrotroph cells with thyrotropin-releasing hormone provoked fusion of vesicles to the plasma membrane, increased expression of Kir3.1 and Kir3.4 subunits in the plasma membrane, and markedly enhanced KG currents stimulated by dopamine and somatostatin. These data indicate a novel mechanism for the rapid insertion of functional ion channels into the plasma membrane, which could form a new type of negative feedback control loop for hormone secretion in the endocrine system.  (+info)

Molecular determinants for sodium-dependent activation of G protein-gated K+ channels. (5/480)

G protein-gated inwardly rectifying K+ channels (GIRKs) are activated by a direct interaction with Gbetagamma subunits and also by raised internal [Na+]. Both processes require the presence of phosphatidylinositol bisphosphate (PIP2). Here we show that the proximal C-terminal region of GIRK2 mediates the Na+-dependent activation of both the GIRK2 homomeric channels and the GIRK1/GIRK2 heteromeric channels. Within this region, GIRK2 has an aspartate at position 226, whereas GIRK1 has an asparagine at the equivalent position (217). A single point mutation, D226N, in GIRK2, abolished the Na+-dependent activation of both the homomeric and heteromeric channels. Neutralizing a nearby negative charge, E234S had no effect. The reverse mutation in GIRK1, N217D, was sufficient to restore Na+-dependent activation to the GIRK1N217D/GIRK2D226N heteromeric channels. The D226N mutation did not alter either the single channel properties or the ability of these channels to be activated via the m2-muscarinic receptor. PIP2 dramatically increased the open probability of GIRK1/GIRK2 channels in the absence of Na+ or Gbetagamma but did not preclude further activation by Na+, suggesting that Na+ is not acting simply to promote PIP2 binding to GIRKs. We conclude that aspartate 226 in GIRK2 plays a crucial role in Na+-dependent gating of GIRK1/GIRK2 channels.  (+info)

Identification of a potassium channel site that interacts with G protein betagamma subunits to mediate agonist-induced signaling. (6/480)

Activation of heterotrimeric GTP-binding (G) proteins by their coupled receptors, causes dissociation of the G protein alpha and betagamma subunits. Gbetagamma subunits interact directly with G protein-gated inwardly rectifying K+ (GIRK) channels to stimulate their activity. In addition, free Gbetagamma subunits, resulting from agonist-independent dissociation of G protein subunits, can account for a major component of the basal channel activity. Using a series of chimeric constructs between GIRK4 and a Gbetagamma-insensitive K+ channel, IRK1, we have identified a critical site of interaction of GIRK with Gbetagamma. Mutation of Leu339 to Glu within this site impaired agonist-induced sensitivity and decreased binding to Gbetagamma, without removing the Gbetagamma contribution to basal currents. Mutation of the corresponding residue in GIRK1 (Leu333) resulted in a similar phenotype. Both the GIRK1 and GIRK4 subunits contributed equally to the agonist-induced sensitivity of the heteromultimeric channel. Thus, we have identified a channel site that interacts specifically with Gbetagamma subunits released through receptor stimulation.  (+info)

Bombesin receptors inhibit G protein-coupled inwardly rectifying K+ channels expressed in Xenopus oocytes through a protein kinase C-dependent pathway. (7/480)

Although activation of G protein-coupled inward rectifying K+ (GIRK) channels by Gi/Go-coupled receptors has been shown to be important in postsynaptic inhibition in the central nervous system, there is also evidence to suggest that inhibition of GIRK channels by Gq-coupled receptors is involved in postsynaptic excitation. In the present study we addressed whether the Gq-coupled receptors of the bombesin family can couple to GIRK channels and examined the mechanism by which this process occurs. Different combinations of GIRK channel subunits (Kir3.1, Kir3.2, and Kir3.4) and bombesin receptors (BB1 and BB2) were expressed in Xenopus oocytes. In all combinations tested GIRK currents were reversibly inhibited upon application of the bombesin-related peptides, neuromedin B or gastrin-releasing peptide in a concentration-dependent manner. Incubation of oocytes in the phospholipase C inhibitor U73122 or the protein kinase C (PKC) inhibitors chelerythrine and staurosporine significantly reduced the inhibition of GIRK currents by neuromedin B, whereas the Ca2+ chelator, BAPTA-AM had no effect. The involvement of PKC was further demonstrated by direct inhibition of GIRK currents by the phorbol esters, phorbol-12,13-dibutyrate and phorbol-12-myristate-13-acetate. In contrast, the inactive phorbol ester 4alpha-phorbol and protein kinase A activators, forskolin and 8-bromo cAMP did not inhibit GIRK currents. At the single-channel level, direct activation of PKC using phorbol ester phorbol-12, 13-dibutyrate caused a dramatic reduction in open probability of GIRK channels due to an increase in duration of the interburst interval.  (+info)

Effect of extracellular cations on the inward rectifying K+ channels Kir2.1 and Kir3.1/Kir3.4. (8/480)

The effects of Ba2+, Mg2+, Ca2+ and Na+ as blocking ions were investigated in 90 and 10 mM extracellular K+ solutions on the cloned inward rectifying K+ channel Kir2.1 expressed in Xenopus oocytes. Some data were also obtained using another inward rectifying K+ channel Kir3.1/Kir3.4. The addition of Ba2+ caused a concentration-, voltage- and time-dependent block of both channels. Decreasing the extracellular K+ concentration augmented the block. The data suggest that Ba2+ blocks the channels by binding to a site within the channel pore and that the electrical binding distance, delta, of the site is significantly different for Kir2.1 and Kir3. 1/Kir3.4 (0.38 and 0.22, respectively). Mg2+ and Ca2+ caused an instantaneous concentration- and voltage-dependent block of both channels. With Kir2.1, decreasing the K+ concentration augmented the block. The voltage dependence of the block was less than that of Ba2+ ([delta], 0.1), indicating a more superficial binding site for these ions within the channel pore. The affinity of the channels for Mg2+ and Ca2+ was 1000-fold lower than that for Ba2+. Addition of Na+ resulted in a concentration-, voltage- and time-dependent block of Kir2.1, similar to that observed with Ba2+. The competition between the blocking cations (for Kir2.1: Ba2+, Mg2+, Ca2+; for Kir3. 1/Kir3.4: Ba2+) and extracellular K+ suggests that the binding sites for the blocking cations may be sites to which K+ binds as part of the normal passage of K+ through the channels. It is possible that under normal physiological conditions naturally occurring extracellular cations may partly block the two inward rectifying K+ channels.  (+info)

Potassium inwardly-rectifying channel, subfamily J, member 3, also known as KCNJ3 or Kir3.1, is a human gene. Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and plays an important role in regulating heartbeat. It associates with three other G-protein-activated potassium channels to form a hetero-tetrameric pore-forming complex. KCNJ3 has been shown to interact with KCNJ5. G protein-coupled inwardly-rectifying potassium channel Inward-rectifier potassium ion channel GRCh38: Ensembl release 89: ENSG00000162989 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000026824 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". "Entrez Gene: KCNJ3 ...
Although it has been known for nearly 20 yr that PIP2 is required for activation of GIRK channels (Huang et al., 1998; Sui et al., 1998), the structural details of how the association of PIP2 with GIRK channels leads to channel activation remain poorly described. The initial crystal structures of Kir2.2 and GIRK2 channels provided snapshots of how PIP2 binds to Kir channels, implicating positively charged, basic amino acids in the tether helix, the M2 TMD, and the N-terminal domain in the binding of one PIP2 molecule (Hansen et al., 2011; Whorton and MacKinnon, 2011, 2013). Indeed, a comparison of the amino acids in the tether helix among different Kir channels reveals a high degree of conservation among these basic residues (Fig. S1 a). However, atomic resolution structures are static and lack the dynamic interactions of ligands associating with the channel and inducing gating conformations. In the current study, we combined functional studies with MD simulations to provide evidence for a ...
Tipepidine (INN) (brand names Asverin, Antupex, Asvelik, Asvex, Bitiodin, Cofdenin A, Hustel, Nodal, Sotal), also known as tipepidine hibenzate (JAN), is a synthetic, non-opioid antitussive and expectorant of the thiambutene class. It acts as an inhibitor of G protein-coupled inwardly-rectifying potassium channels (GIRKs). The drug was discovered in the 1950s, and was developed in Japan in 1959. It is used as the hibenzate and citrate salts. The usual dose is 20 mg every 4-6 hours.[citation needed] Possible side effects of tipepidine, especially in overdose, may include drowsiness, vertigo, delirium, disorientation, loss of consciousness, and confusion. Tipepidine has recently garnered interest as a potential psychiatric drug. It is being investigated in depression, obsessive-compulsive disorder, and attention-deficit hyperactivity disorder (ADHD). Through inhibition of GIRK channels, tipepidine increases dopamine levels in the nucleus accumbens, but without increasing locomotor activity or ...
1N9P: Structural Basis of Inward Rectification: Cytoplasmic Pore of the G Protein-Gated Inward Rectifier GIRK1 at 1.8 A Resolution
We measured the impact of genetic ablation of GIRK1, GIRK2 and GIRK3 in mice using established behavioral paradigms. Assays were chosen that would provide insight into the contribution of GIRK channels to activity, anxiety, muscle co-ordination, ataxia and reward-related behavior. We found that GIRK1−/− mice and GIRK2−/− mice often displayed robust and similar phenotypes, including elevated open-field activity, decreased anxiety-like behavior, decreased baclofen ataxia and increased operant responding for food.. Overall, GIRK2−/− mice exhibited the most pronounced phenotypes in this study. These observations are consistent with the view that GIRK2 contributes to channel formation in most neuron populations that exhibit a GIRK conductance (Cruz et al. 2004; Koyrakh et al. 2005; Luscher et al. 1997; Slesinger et al. 1997; Torrecilla et al. 2002). GIRK2−/− mice have displayed phenotypes in many behavioral tests. For example, GIRK2−/− mice displayed blunted behavioral responses ...
Previous data from our laboratory has indicated that there is a functional link between the β-adrenergic receptor signaling pathway and the G-protein inwardly rectifying potassium channel (GIRK1) in human breast cancer cell lines. We wanted to determine if GIRK channels were expressed in lung cancers and if a similar link exists in lung cancer. GIRK1-4 expression and levels were determined by reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR. GIRK protein levels were determined by western blots and cell proliferation was determined by a 5-bromo-2-deoxyuridine (BrdU) assay. GIRK1 mRNA was expressed in three of six small cell lung cancer (SCLC) cell lines, and either GIRK2, 3 or 4 mRNA expression was detected in all six SCLC cell lines. Treatment of NCI-H69 with β2-adrenergic antagonist ICI 118,551 (100 μM) daily for seven days led to slight decreases of GIRK1 mRNA expression levels. Treatment of NCI-H69 with the β-adrenergic agonist isoproterenol (10 μM) decreased growth
TY - JOUR. T1 - Discovery, synthesis and characterization of a series of (1-alkyl-3-methyl-1H-pyrazol-5-yl)-2-(5-aryl-2H-tetrazol-2-yl)acetamides as novel GIRK1/2 potassium channel activators. AU - Sharma, Swagat. AU - Kozek, Krystian A.. AU - Abney, Kristopher K.. AU - Kumar, Sushil. AU - Gautam, Nagsen. AU - Alnouti, Yazen. AU - David Weaver, C.. AU - Hopkins, Corey R.. PY - 2019/3/15. Y1 - 2019/3/15. N2 - The present study describes the discovery and characterization of a series of 5-aryl-2H-tetrazol-3-ylacetamides as G protein-gated inwardly-rectifying potassium (GIRK) channels activators. Working from an initial hit discovered during a high-throughput screening campaign, we identified a tetrazole scaffold that shifts away from the previously reported urea-based scaffolds while remaining effective GIRK1/2 channel activators. In addition, we evaluated the compounds in Tier 1 DMPK assays and have identified a (3-methyl-1H-pyrazol-1-yl)tetrahydrothiophene-1,1-dioxide head group that imparts ...
G protein-gated inwardly-rectifying potassium ion channels (GIRK) mediate the postsynaptic inhibitory effect of many neurotransmitters and related drugs of abus...
View mouse Kcnj2 Chr11:111066164-111076821 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
View mouse Kcnj16 Chr11:110968033-111027968 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
Reaktivität: Fledermaus, Rind (Kuh), Hund and more. 88 verschiedene KCNJ1 Antikörper vergleichen. Alle direkt auf antikörper-online bestellbar!
TY - JOUR. T1 - Quantitative analysis of mammalian GIRK2 channel regulation by G proteins, the signaling lipid PIP2 and Na+ in a reconstituted system. AU - Wang, Weiwei. AU - Whorton, Matthew R.. AU - MacKinnon, Roderick. PY - 2014. Y1 - 2014. N2 - GIRK channels control spike frequency in atrial pacemaker cells and inhibitory potentials in neurons. By directly responding to G proteins, PIP2 and Na(+), GIRK is under the control of multiple signaling pathways. In this study, the mammalian GIRK2 channel has been purified and reconstituted in planar lipid membranes and effects of Gα, Gβγ, PIP2 and Na(+) analyzed. Gβγ and PIP2 must be present simultaneously to activate GIRK2. Na(+) is not essential but modulates the effect of Gβγ and PIP2 over physiological concentrations. Gαi1(GTPγS) has no effect, whereas Gαi1(GDP) closes the channel through removal of Gβγ. In the presence of Gβγ, GIRK2 opens as a function of PIP2 mole fraction with Hill coefficient 2.5 and an affinity that poises ...
KIR3.4 antibody (potassium inwardly-rectifying channel, subfamily J, member 5) for ICC/IF, IHC, WB. Anti-KIR3.4 pAb (GTX54780) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
TY - JOUR. T1 - Epistatic interaction of CREB1 and KCNJ6 on rumination and negative emotionality. AU - Lazary, Judit. AU - Juhasz, Gabriella. AU - Anderson, Ian M.. AU - Jacob, Christian P.. AU - Nguyen, T. Trang. AU - Lesch, Klaus Peter. AU - Reif, Andreas. AU - Deakin, J. F.William. AU - Bagdy, Gyorgy. PY - 2011/1/1. Y1 - 2011/1/1. N2 - G protein-activated K+ channel 2 (GIRK2) and cAMP-response element binding protein (CREB1) are involved in synaptic plasticity and their genes have been implicated depression and memory processing. Excessive rumination is a core cognitive feature of depression which is also present in remission. High scores on the Ruminative Response Scale (RRS) questionnaire are predictive of relapse and recurrence. Since rumination involves memory, we tested the hypothesis that variation in the genes encoding GIRK2 (KCNJ6) and CREB1 mechanisms would influence RRS scores. GIRK2 and CREB1 polymorphisms were studied in two independent samples (n = 651 and n = 1174) from the ...
Nakamura A, Fujita M, Ono H, Hongo Y, Kanbara T, Ogawa K, Morioka Y, Nishiyori A, Shibasaki M, Mori T, Suzuki T, Sakaguchi G, Kato A, Hasegawa ...
TY - JOUR. T1 - Molecular basis of downregulation of G-protein -coupled inward rectifying k+ current (ik,ach) in chronic human atrial fibrillation decrease in GIRK4 mrna correlates with reduced IK,ACh and muscarinic receptor-mediated shortening of action potentials. AU - Dobrev, Dobromir. AU - Graf, E.. AU - Wettwer, E.. AU - Himmel, H. M.. AU - Hála, O.. AU - Doerfel, C.. AU - Christ, T.. AU - Schüler, S.. AU - Ravens, U.. PY - 2001/11/20. Y1 - 2001/11/20. N2 - Background - Clinical and experimental evidence suggest that the parasympathetic nervous system is involved in the pathogenesis of atrial fibrillation (AF). However, it is unclear whether changes in G-protein-coupled inward rectifying K+ current (IK,ACh) contribute to chronic AF. Methods and Results - In the present study, we used electrophysiological recordings and competitive reverse-transcription polymerase chain reaction to study changes in IK,ACh and the level of the IK,ACh GIRK4 subunit in isolated human atrial myocytes and the ...
If SDF-1 acts downstream via GIRK channels, one would predict a change in GnRH neuronal movement in the presence of TPN-Q in +MNC explants (endogenous SDF-1 in midline cells) and no effect in −MNC explants (express little or no endogenous SDF-1). As predicted, a significant decrease in cell speed (15%) was seen when GIRK channels were blocked by TPN-Q (100 nM) in +MNC explants, while no differences in speed were detected after TPN-Q application in NPE-MNC explants (Table 4). These data are consistent with SDF-1 acting via GIRK channels to alter cell movement.. To further test if SDF signaling activates GIRK channels, −MNC explants were analyzed pre- and post-application of SDF-1 or SDF-1+TPN-Q. There was a significant decrease in TDS (23%) when TPN-Q was added with SDF-1, as compared to SDF-1 alone (Table 4; Fig. 3L), but these values were similar to the speed in the control condition (SFM, P,0.05). These data support the hypothesis that SDF-1/CXCR4-mediated movement is signaled via GIRK ...
HEK293-HuCACNA1C/NEUROD1/CACNA2D1/KCNJ2 cell line is a hypotriploid human cell line, which has been transfected with a human calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C), a human neuronal differentiation 1 (NEUROD1), a human calcium channel, voltage-dependent, alpha 2/delta subunit 1 (CACNA2D1) and a human potassium inwardly-rectifying channel, subfamily J, member 2 (KCNJ2) to allow stably express of the human CACNA1C, NEUROD1, CACNA2D1 and KCNJ2. It is an example of a cell line tr
A number of studies have been performed to identify the association between potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) gene and type 2 diabetes mellitus (T2DM) in East Asia
Weaver mice have a severe hypoplasia of the cerebellum with an almost complete loss of the midline granule cells. Recent genetic studies of weaver mice have identified a mutation resulting in an amino acid substitution (G156S) in the pore of the inwardly rectifying potassium channel subunit Kir 3.2. When expressed in Xenopus oocytes the weaver mutation alters channel selectivity from a potassium-selective to a nonspecific cation-selective pore. In this study we confirm by cell-attached patch-clamp recording that the mutation produces a non-selective cation channel. We also demonstrate that the cell death induced by weaver expression may be prevented by elimination of calcium from the extracellular solution as well as by coexpression with the wild-type Kir 3.2 allele, or other members of the Kir 3.0 subfamily. These results suggest that the weaver defect in Kir 3.2 may cause cerebellar cell death by cell swelling and calcium overload. Cells which express the weaver subunit, but which normally survive,
In the present study, we conducted: (i) in situ hybridization in order to investigate the expression of kainate and GABA(A) receptor subunits and the pre-proenkephalin and prodynorphin peptides in the brain of weaver mouse (a genetic model of dopamine deficiency) and (ii) immunocytochemistry in order to study the somatostatin-positive cells in weaver striatum. Our results indicated: (i) increases in mRNA levels of KA2 and GluR6 kainate receptor subunits, of alpha(4) and beta(3) GABA(A) receptor subunits and of pre-proenkephalin and prodynorphin in 6-month-old weaver striatum; (ii) a decrease in alpha(1) and beta(2) GABA(A) subunit mRNAs in 6-month-old weaver globus pallidus; (iii) increases in KA2, alpha(4) and beta(3) and decreases in alpha(2) and beta(2) mRNAs in the 6-month-old weaver somatosensory cortex; and (iv) an increase in somatostatin-immunopositive cells in 3-month-old weaver striatum. We suggest that: (i) in striatum, the alterations are induced by the induction of the transcription ...
Overexpression the KCNJ3, a gene that encodes subunit 1 of G-protein activated inwardly rectifying K+ channel (GIRK1) in the primary tumor has been found to be associated with reduced survival times and increased lymph node metastasis in breast cancer patients. In order to survey possible tumorigenic properties of GIRK1 overexpression, a range of malignant mammary epithelial cells, based on the MCF-7 cell line that permanently overexpress different splice variants of the KCNJ3 gene (GIRK1a, GIRK1c, GIRK1d and as a control, eYFP) were produced. Subsequently, selected cardinal neoplasia associated cellular parameters were assessed and compared. Adhesion to fibronectin coated surface as well as cell proliferation remained unaffected. Other vital parameters intimately linked to malignancy, i.e. wound healing, chemoinvasion, cellular velocities / motilities and angiogenesis were massively affected by GIRK1 overexpression. Overexpression of different GIRK1 splice variants exerted differential actions. While
Several inwardly-rectifying (Kir) potassium channels (Kin l 1, Kir41 and Kir4 2) are characterised by their sensitivity to inhibition by intracellular H+ within the physiological range The mechanism by which these channels are regulated by intracellular pH has been the subject of intense scrutiny for over a decade, yet the molecular identity of the titratable pH-sensor remains elusive In this study we have taken advantage of the acidic intracellular environment of S cerevisiae and used a K+-auxotrophic strain to screen for mutants of Kin 1 1 with impaired pH-sensitivity In addition to the previously identified K80M mutation, this unbiased screening approach identified a novel mutation (S172T) in the second transmembrane domain (TM2) that also produces a marked reduction in pH-sensitivity through destabilization of the closed-state However, despite this extensive mutagenic approach, no mutations could be identified which removed channel pH-sensitivity or which were likely to act as a separate H+-sensor
Gene Information Potassium channels are present in most mammalian cells where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein which has a greater tendency to allow potassium to flow into a cell rather than out of a cell is controlled by G-proteins. It associates with another G-protein-activated potassium channel to form a heteromultimeric pore-forming complex. [provided by RefSeq Jul 2008]. ...
KCNJ4 - KCNJ4 (Myc-DDK-tagged)-Human potassium inwardly-rectifying channel, subfamily J, member 4 (KCNJ4), transcript variant 2 available for purchase from OriGene - Your Gene Company.
KCNJ6 - KCNJ6 (Myc-DDK-tagged)-Human potassium inwardly-rectifying channel, subfamily J, member 6 (KCNJ6) available for purchase from OriGene - Your Gene Company.
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Purpose: The inwardly-rectifying potassium channel Kir7.1 is present in the apical processes of retinal pigment epithelial (RPE) cells. Several mutations in the gene that encodes Kir7.1 (KCNJ13) cause blindness in the allelic disorders of Snowflake Vitreoretinal Degeneration (SVD) and Lebers Congenital Amaurosis (LCA16). In this study, we treated two Kir7.1 nonsense mutations that result in LCA16 (W53X and R166X) with the read-through compounds Ataluren (PTC-124; AdooQ Biosciences) and a novel small molecule, RTC-14.. Methods: Chinese Hamster Ovary (CHO-K1) cells were transfected with N-terminal GFP-fused W53X and R166X mutant plasmids. The cells were then treated with two different concentrations, 5 µM and 10 µM, of the read-through compounds PTC-124 or RTC-14 after eight hours of transfection, and the cells were incubated with these drugs for 36 hours. Whole-cell patch clamp electrophysiology was performed on the transfected cells. Function of the Kir7.1 channel was measured in the presence ...
Berlin, S., Hadad, E., Heled, Y., and Moran, D.S. (2004). The Efficacy of Nutritional Supplements upon Physical Exercise. Journal of Israeli Military Medicine 1(2), 72-80.. Berlin, S., Shalit, L., Yarom, Y., and Moran, D.S. (2007). Metabolic rate prediction by massless actigraphy for outdoor activities. Mil Med 172, 882-887.. Eliyahu, U., Berlin, S., Hadad, E., Heled, Y., and Moran, D.S. (2007). Psychostimulants and military operations. Mil Med 172, 383-387.. Rubinstein, M., Peleg, S., Berlin, S., Brass, D., and Dascal, N. (2007). Galphai3 primes the G protein-activated K+ channels for activation by coexpressed Gbetagamma in intact Xenopus oocytes. J Physiol 581, 17-32.. Berlin S. (2009). Do bigger and "better" labs have easier access to high impact factor journals? Science signaling. December 9th, E-letter. http://stke.sciencemag.org/content/2/99/eg15.e-letters (Addition to Living by The Numbers- Michael B. Yaffe; 01 Dec 2009: Vol. 2, Issue 99, pp. eg15, doi: 10.1126/scisignal.299eg15).. Lvov, ...
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Eagles fullback Leonard Weaver has become among the first players to publicly weigh in on the McNabb trade situation. - Daily News staff, Philadelphia Daily News
Roboticists have begun to design biologically inspired robots with soft or partially soft bodies, which have the potential to be more robust and adaptable, and safer for human interaction, than traditional rigid robots ...
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Bladder cancer (BC) is the ninth most common cancer and the 13th most common cause of cancer death. Although p21 protein-activated kinase (PAK) regulates cell growth, motility, and morphology, the...
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Aldosterone-producing adenomas (APAs) cause a sporadic form of primary aldosteronism and somatic mutations in the KCNJ5 gene, which encodes the G-protein-activated inward rectifier K+ channel 4, GIRK4, account for ≈40% of APAs. Additional somatic APA mutations were identified recently in 2 other genes, ATP1A1 and ATP2B3, encoding Na+/K+-ATPase 1 and Ca2+-ATPase 3, respectively, at a combined prevalence of 6.8%. We have screened 112 APAs for mutations in known hotspots for genetic alterations associated with primary aldosteronism. Somatic mutations in ATP1A1, ATP2B3, and KCNJ5 were present in 6.3%, 0.9%, and 39.3% of APAs, respectively, and included 2 novel mutations (Na+/K+-ATPase p.Gly99Arg and GIRK4 p.Trp126Arg). CYP11B2 gene expression was higher in APAs harboring ATP1A1 and ATP2B3 mutations compared with those without these or KCNJ5 mutations. Overexpression of Na+/K+-ATPase p.Gly99Arg and GIRK4 p.Trp126Arg in HAC15 adrenal cells resulted in upregulation of CYP11B2 gene expression and its ...
A channel that is "inwardly-rectifying" is one that passes current (positive charge) more easily in the inward direction (into the cell) than in the outward direction (out of the cell). It is thought that this current may play an important role in regulating neuronal activity, by helping to stabilize the resting membrane potential of the cell. By convention, inward current (positive charge moving into the cell) is displayed in voltage clamp as a downward deflection, while an outward current (positive charge moving out of the cell) is shown as an upward deflection. At membrane potentials negative to potassiums reversal potential, inwardly rectifying K+ channels support the flow of positively charged K+ ions into the cell, pushing the membrane potential back to the resting potential. This can be seen in figure 1: when the membrane potential is clamped negative to the channels resting potential (e.g. -60 mV), inward current flows (i.e. positive charge flows into the cell). However, when the ...
Research Grant Recipient: Jennifer Westendorf, PhD. Award Value: $250,000. Research Focus: Osteoarthritis. Project Summary: This project will help determine how proteins called Girk2 and Girk3 contribute to cartilage formation and repair in the setting of osteoarthritis. The investigators believe that osteoarthritis can be prevented if these proteins are absent or inactive. This work will lead to the development of better strategies to treat osteoarthritis.. Dr. Westendorf studies the molecular the epigenetic basis for skeltal formation, the regeneration of bone and cartilage, and the growth of pirmary and metastatic bone tumors. She is the vice chair of the Department of Biochemistry and Molecular Biology, and a consultant for the Department of Orthopedic Surgery at Mayo Clinic.. ...
DCAT: At the organizations annual membership meeting DCAT installed Dix Weaver, Sr. supply chain consultant at Eli Lilly and company as the new president of the organization for 2008. Mr. Weaver succeeds Joe Colleluori, Lonza Inc. and is
Expression of KCNJ6 (BIR1, GIRK2, hiGIRK2, KATP2, KCNJ7, Kir3.2) in hippocampus tissue. Antibody staining with in immunohistochemistry.
Expression of KCNJ6 (BIR1, GIRK2, hiGIRK2, KATP2, KCNJ7, Kir3.2) in ovary tissue. Antibody staining with in immunohistochemistry.
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When it comes to pain, guys may be tougher than gals because they have more of a particular type of protein, new research suggests. Two studies published online this week by the Proceedings of the National Academy of Sciences implicate proteins known as GIRKs in sex-based differences in pain sensitivity in mice. The findings could help researchers develop new gender-specific treatments for discomfort. Previous research had shown that males tend to have a higher threshold for pain than females do and that medications affect the sexes differently, although the precise mechanism remained unclear. In the new work, scientists tested analgesic drugs on mice unable to produce the GIRK2 protein. Allan I. Basbaum of Rockefeller University and his colleagues found that male mutants had lower pain thresholds than normal male mice. Female mutants exhibited a tolerance comparable to that of their normal counterparts, however, suggesting that GIRK2 is responsible for sex differences in pain sensitivity. Male ...
A budget friendly kit of Kir channel antibodies from Alomone Labs, ideal for screening purposes. An economical way to sample Abs. Control antigens included. Lyophilized. Worldwide shipping at room temperature. Top supplier for inward rectifier K+ channel research! Join the thousands of researchers using our products.
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Mechanism of GIRK Activation. P2Y1 -mediated activation of IGIRK was PTX-sensitive and strongly inhibited by over-expressing the Gβγ-scavenging protein, Gα-transducin. This implies that-as for GIRK-activation by α2 adrenoceptors or M2 muscarinic receptors in these neurons (Ruiz-Velasco and Ikeda, 1998; Fernandez-Fernandez et al., 2001)-P2Y-induced activation is mediated by βγ-subunits liberated from stimulated Gi protein heterotrimers. This accords with the mechanism of GIRK activation by G protein-coupled receptors deduced from many other studies (see Wickman and Clapham, 1995; Stanfield et al., 2002).. Mechanism of GIRK Inhibition. In contrast, IGIRK inhibition by P2Y receptors is probably mediated by the α-subunit of Gq/11 because 1) it was attenuated by RGS2, which specifically interacts with Gαq/11 (Heximer et al., 1997), and 2) was unaffected by RGS11, which interacts with Gβq (see Results) (Lei et al., 2000, 2001). This corresponds with the most likely G protein-coupling required ...
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G protein-coupled inwardly-rectifying potassium channel Inward-rectifier potassium ion channel GRCh38: Ensembl release 89: ... "A recombinant inwardly rectifying potassium channel coupled to GTP-binding proteins". The Journal of General Physiology. 107 (3 ... "G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase". The ... "Diverse trafficking patterns due to multiple traffic motifs in G protein-activated inwardly rectifying potassium channels from ...
A G protein-coupled inwardly-rectifying potassium channel, abbreviated as GIRK.. ...
It acts as an inhibitor of G protein-coupled inwardly-rectifying potassium channels (GIRKs). The drug was discovered in the ... "A Novel Antidepressant-like Action of Drugs Possessing GIRK Channel Blocking Action in Rats". Yakugaku Zasshi. 130 (5): 699-705 ... Through inhibition of GIRK channels, tipepidine increases dopamine levels in the nucleus accumbens, but without increasing ... "Tipepidine activates VTA dopamine neuron via inhibiting dopamine D₂ receptor-mediated inward rectifying K⁺ current". ...
G protein-coupled inwardly-rectifying potassium channel Inward-rectifier potassium ion channel GRCh38: Ensembl release 89: ... "G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase". J. Biol. ... "G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase". J. Biol. ... Liao YJ, Jan YN, Jan LY (1996). "Heteromultimerization of G-protein-gated inwardly rectifying K+ channel proteins GIRK1 and ...
Embedded in the cell membrane is also the G protein-coupled inwardly-rectifying potassium channel. When a Gβγ or Gα(GTP) ... Yamada M, Inanobe A, Kurachi Y (December 1998). "G protein regulation of potassium ion channels". Pharmacological Reviews. 50 ( ... The activation of the potassium channel and subsequent deactivation of the calcium channel causes membrane hyperpolarization. ... molecule binds to the C-terminus of the potassium channel, it becomes active, and potassium ions are pumped out of the neuron. ...
G protein-coupled inwardly-rectifying potassium channel Inward-rectifier potassium ion channel GRCh38: Ensembl release 89: ... "G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase". The ... "G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase". The ... Plummer HK, Dhar MS, Cekanova M, Schuller HM (2006). "Expression of G-protein inwardly rectifying potassium channels (GIRKs) in ...
G protein-coupled inwardly-rectifying potassium channel Inward-rectifier potassium ion channel GRCh38: Ensembl release 89: ... 1994). "Human G-protein-coupled inwardly rectifying potassium channel (GIRK1) gene (KCNJ3): localization to chromosome 2 and ... 1996). "A recombinant inwardly rectifying potassium channel coupled to GTP- binding proteins". J. Gen. Physiol. 107 (3): 381-97 ... 2003). "G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase". J ...
... and P/Q-type calcium channels and activate inwardly rectifying potassium channels. CB1 antagonists produce inverse ... CB1 receptors are coupled through Gi/o proteins and inhibit adenylyl cyclase and activate mitogen-activated protein (MAP) ... Both receptors are 7-transmembrane G-protein coupled receptors (GPCRs) which inhibit the accumulation of cyclic adenosine ...
"Neuronal inwardly rectifying K(+) channels differentially couple to PDZ proteins of the PSD-95/SAP90 family". J. Neurosci. 20 ( ... Potassium inwardly-rectifying channel, subfamily J, member 4, also known as KCNJ4 or Kir2.3, is a human gene. Several different ... "Neuronal inwardly rectifying K(+) channels differentially couple to PDZ proteins of the PSD-95/SAP90 family". J. Neurosci. 20 ( ... The latter are referred to as inwardly rectifying K+ channels, and they have a greater tendency to allow potassium to flow into ...
"Endocannabinoids modulate N-type calcium channels and G-protein-coupled inwardly rectifying potassium channels via CB1 ... the two most commonly coupled G-proteins to cannabinoid receptors, has been shown to modulate potassium channel activity. ... "Co-expression of the voltage-gated potassium channel Kv1.4 with transient receptor potential channels (TRPV1 and TRPV2) and the ... The cannabinoid receptors CB1 and CB2, two G protein-coupled receptors that are located in the central and peripheral nervous ...
... to reduce the firing rate of neurons through direct activation of G protein-coupled inwardly-rectifying potassium channels. ... tonically activates inwardly rectifying K(+) channels, which reduces the basal firing frequency of dopamine (DA) neurons of the ... to open the ion channel. Image legend Ion channel G proteins & linked receptors (Text color) Transcription factors United ... Methamphetamine has been identified as a potent full agonist of trace amine-associated receptor 1 (TAAR1), a G protein-coupled ...
Through direct activation of G protein-coupled inwardly-rectifying potassium channels, TAAR1 reduces the firing rate of ... a Gs-coupled and Gq-coupled G protein-coupled receptor (GPCR) discovered in 2001, which is important for regulation of brain ... tonically activates inwardly rectifying K(+) channels, which reduces the basal firing frequency of dopamine (DA) neurons of the ... Image legend Ion channel G proteins & linked receptors (Text color) Transcription factors Malenka RC, Nestler EJ, Hyman SE, ...
Examples include coupling to and activating G protein-coupled inwardly-rectifying potassium channels. ... Whereas G proteins are activated by G protein-coupled receptors, they are inactivated by RGS proteins (for "Regulator of G ... Heterotrimeric G proteins, sometimes referred to as the "large" G proteins, are activated by G protein-coupled receptors and ... G protein-coupled receptors, G proteins, second messengers, the enzymes that trigger protein phosphorylation in response to ...
Through direct activation of G protein-coupled inwardly-rectifying potassium channels (GIRKs), TAAR1 can reduce the firing rate ... TAAR1 is an amine-activated Gs-coupled and Gq-coupled G protein-coupled receptor (GPCR) that is primarily located in several ... Upon entering the presynaptic neuron, these compounds activate TAAR1 which, through protein kinase A (PKA) and protein kinase C ... and the DA D2R-coupled, G protein-independent AKT/GSK3 signaling pathway (Espinoza et al., 2015; Harmeier et al., 2015), such ...
Embedded in the cell membrane is also the G protein-coupled inwardly-rectifying potassium channel. When a Gβγ or Gα(GTP) ... Yamada M, Inanobe A, Kurachi Y (December 1998). "G protein regulation of potassium ion channels". Pharmacological Reviews. 50 ( ... Philip F, Sengupta P, Scarlata S (June 2007). "Signaling through a G Protein-coupled receptor and its corresponding G protein ... The activation of the potassium channel and subsequent deactivation of the calcium channel causes membrane hyperpolarization. ...
2000). "Neuronal inwardly rectifying K(+) channels differentially couple to PDZ proteins of the PSD-95/SAP90 family". J. ... Dart C, Leyland ML (2001). "Targeting of an A kinase-anchoring protein, AKAP79, to an inwardly rectifying potassium channel, ... "Neuronal inwardly rectifying K(+) channels differentially couple to PDZ proteins of the PSD-95/SAP90 family". J. Neurosci. 20 ( ... Rae JL, Shepard AR (1998). "Inwardly rectifying potassium channels in lens epithelium are from the IRK1 (Kir 2.1) family". Exp ...
Positively to inwardly rectifying and A-type outward potassium channels. Negatively to D-type outward potassium channels ... The receptor may exist as a homodimer or form heterodimers or other GPCR oligomers with different classes of G-protein-coupled ... including the positively influenced inwardly rectifying potassium channels (=Kir or IRK), and calcium channels, which are ... The cannabinoid type 1 receptor, often abbreviated as CB1, is a G protein-coupled cannabinoid receptor located primarily in the ...
"Neuronal inwardly rectifying K(+) channels differentially couple to PDZ proteins of the PSD-95/SAP90 family". J. Neurosci. 20 ( ... With PSD-93 it is recruited into the same NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact ... PSD-95 (postsynaptic density protein 95) also known as SAP-90 (synapse-associated protein 90) is a protein that in humans is ... "Protein trafficking and anchoring complexes revealed by proteomic analysis of inward rectifier potassium channel (Kir2.x)- ...
Neuroscience portal G protein-coupled inwardly-rectifying potassium channel Transporter Classification Database hERG Kubo Y, ... At membrane potentials negative to potassium's reversal potential, inwardly rectifying K+ channels support the flow of ... Abraham MR, Jahangir A, Alekseev AE, Terzic A (November 1999). "Channelopathies of inwardly rectifying potassium channels". ... Nomenclature and Molecular Relationships of Inwardly Rectifying Potassium Channels". Pharmacological Reviews. 57 (4): 509-26. ...
... potassium channels, inwardly rectifying MeSH D12.776.543.550.425.750.450.500 -- g protein-coupled inwardly-rectifying potassium ... potassium channels, inwardly rectifying MeSH D12.776.543.585.400.750.450.500 -- g protein-coupled inwardly-rectifying potassium ... shab potassium channels MeSH D12.776.543.550.425.750.900.249 -- ether-a-go-go potassium channels MeSH D12.776.543.550.425.750. ... shab potassium channels MeSH D12.776.543.585.400.750.900.249 -- ether-a-go-go potassium channels MeSH D12.776.543.585.400.750. ...
"G protein-coupled inwardly rectifying potassium channels are targets of alcohol action" (PDF). Nat. Neurosci. 2 (12): 1084-90. ... Dhar MS, Plummer HK (2006). "Protein expression of G-protein inwardly rectifying potassium channels (GIRK) in breast cancer ... Four G protein gated inwardly-rectifying potassium (GIRK) channel subunits have been identified in mammals: GIRK1, GIRK2, GIRK3 ... G protein-gated ion channels are associated with a specific type of G protein-coupled receptor. These ion channels are ...
G protein-coupled inwardly-rectifying potassium channels are a type of G protein-gated ion channels because of this direct ... The G protein-coupled inwardly-rectifying potassium channels (GIRKs) are a family of inward-rectifier potassium ion channels ... G Protein-Coupled Inwardly-Rectifying Potassium Channels at the US National Library of Medicine Medical Subject Headings (MeSH) ... "The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K+-channel proteins". Nature. 374 ( ...
G protein-coupled inwardly-rectifying potassium channel. *Transporter Classification Database. *hERG. References[edit]. *^ a b ... Inward-rectifier potassium channel. From Wikipedia, the free encyclopedia. (Redirected from Inwardly rectifying potassium ... Figure 1. Whole-cell current recordings of Kir2 inwardly-rectifying potassium channels expressed in an HEK293 cell. (This is a ... "Inwardly Recifying Potassium Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and ...
The primary effectors of Gβγ are various ion channels, such as G-protein-regulated inwardly rectifying K+ channels (GIRKs), P/Q ... Phosphatidylinositol 4,5-bisphosphate (PIP2) binds to and directly activates inwardly rectifying potassium channels (Kir). PIP2 ... Also called G protein-coupled receptor, seven-transmembrane domain receptor, 7 TM receptor, constitute a large protein family ... calcium channel Calcium-activated potassium channel Cyclic nucleotide-gated ion channel Acid-sensing ion channel Ryanodine ...
Endocannabinoids modulate N-type calcium channels and G-protein-coupled inwardly rectifying potassium channels via CB1 ... Co-expression of the voltage-gated potassium channel Kv1.4 with transient receptor potential channels (TRPV1 and TRPV2) and the ... Twitchell W, Brown S, Mackie K , title = Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal ... CB1 cannabinoid receptor activity is modulated by the cannabinoid receptor interacting protein CRIP 1a , journal = Mol. ...
G protein-coupled inwardly-rectifying potassium channel. *Transporter Classification Database. *hERG. References[edit]. *^ a b ... Figure 1. Whole-cell current recordings of Kir2 inwardly-rectifying potassium channels expressed in an HEK293 cell. (This is a ... "Inwardly Recifying Potassium Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and ... At membrane potentials negative to potassium's reversal potential, inwardly rectifying K+ channels support the flow of ...
G protein-coupled inwardly-rectifying potassium channels are a type of G protein-gated ion channels because of this direct ... The G protein-coupled inwardly-rectifying potassium channels (GIRKs) are a family of inward-rectifier potassium ion channels ... G Protein-Coupled Inwardly-Rectifying Potassium Channels at the US National Library of Medicine Medical Subject Headings (MeSH) ... "The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K+-channel proteins". Nature. 374 ( ...
Rapid Activation of Inwardly Rectifying Potassium Channels by Immobile G-Protein-Coupled Receptors. Robert M. Lober, Miguel A. ... 2002) G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase. J ... Rapid Activation of Inwardly Rectifying Potassium Channels by Immobile G-Protein-Coupled Receptors ... Rapid Activation of Inwardly Rectifying Potassium Channels by Immobile G-Protein-Coupled Receptors ...
Potassium Channels as Targets for Ethanol: Studies of G-Protein-Coupled Inwardly Rectifying Potassium Channel 2 (GIRK2) Null ... Potassium Channels as Targets for Ethanol: Studies of G-Protein-Coupled Inwardly Rectifying Potassium Channel 2 (GIRK2) Null ... Potassium Channels as Targets for Ethanol: Studies of G-Protein-Coupled Inwardly Rectifying Potassium Channel 2 (GIRK2) Null ... Potassium Channels as Targets for Ethanol: Studies of G-Protein-Coupled Inwardly Rectifying Potassium Channel 2 (GIRK2) Null ...
Endocannabinoids Modulate N-Type Calcium Channels and G-Protein-Coupled Inwardly Rectifying Potassium Channels via CB1 ... Endocannabinoids Modulate N-Type Calcium Channels and G-Protein-Coupled Inwardly Rectifying Potassium Channels via CB1 ... Endocannabinoids Modulate N-Type Calcium Channels and G-Protein-Coupled Inwardly Rectifying Potassium Channels via CB1 ... Endocannabinoids Modulate N-Type Calcium Channels and G-Protein-Coupled Inwardly Rectifying Potassium Channels via CB1 ...
What is G Protein-Coupled Inwardly-Rectifying Potassium Channels? G Protein-Coupled Inwardly-Rectifying Potassium Channels FAQ. ... define G Protein-Coupled Inwardly-Rectifying Potassium Channels. Explain G Protein-Coupled Inwardly-Rectifying Potassium ... G Protein-Coupled Inwardly-Rectifying Potassium Channels definition. ... G Protein-Coupled Inwardly-Rectifying Potassium Channels. Search: G Protein-Coupled Inwardly-Rectifying Potassium Channels. A ...
A recombinant inwardly rectifying potassium channel coupled to GTP-binding proteins.. Chan KW, Langan MN, Sui JL, Kozak JA, ... The impact of recent ion channel science on the development and use of antiarrhythmic drugs. ...
Examples include coupling to and activating G protein-coupled inwardly-rectifying potassium channels. ... Whereas G proteins are activated by G protein-coupled receptors, they are inactivated by RGS proteins (for "Regulator of G ... Heterotrimeric G proteins, sometimes referred to as the "large" G proteins, are activated by G protein-coupled receptors and ... G protein-coupled receptors, G proteins, second messengers, the enzymes that trigger protein phosphorylation in response to ...
GTPase activating protein. GIRK. G protein-coupled inwardly rectifying potassium channel. GRK. G protein-coupled receptor ... 1997) RGS proteins reconstitute the rapid gating kinetics of Gbetagamma-activated inwardly rectifying K+ channels. Proc Natl ... accelerate the activation as well as the deactivation of receptor-stimulated G protein-coupled inwardly rectifying potassium ( ... 2000) GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins. ...
... voltage-dependent potassium channel subunits Kv1.2/1.4 (Sheng et al., 1993) and G-protein-coupled inwardly rectifying potassium ... 1996) Metabotropic glutamate receptors activate G-protein-coupled inwardly rectifying potassium channels in Xenopus oocytes. J ... 1996) G-protein-gated inward rectifier K+ channel proteins (GIRK1) are present in the soma and dendrites as well as in nerve ... coupled to various calcium, potassium, and nonselective cationic channels (Swartz and Bean, 1992; Crépel et al., 1994; ...
0 (G Protein-Coupled Inwardly-Rectifying Potassium Channels); 0 (Receptors, Muscarinic); N9YNS0M02X (Acetylcholine). ... Head skin stimulation activates a cholinergic pathway which then opens G protein-coupled inward-rectifying potassium channels ( ... G-protein-coupled receptors (GPCRs) play critical roles in regulating brain function. Recent advances have greatly expanded our ... G-Protein-Coupled); 0 (Receptors, Metabotropic Glutamate); 0 (Receptors, Muscarinic); 0 (metabotropic glutamate receptor type 1 ...
HCN channel activity is increased. In addition the G protein-coupled inwardly rectifying potassium channel (GIRK) is no longer ... A description of the G-protein-coupled GABAB receptors is beyond the scope of the present paper. ... GABAA receptors are ligand-gated ion channels with chloride conductance. The functional channel is typically heteropentameric ... they must rely on synaptic input mediated by both ionotropic and G-protein-coupled receptors for controlling their firing [24- ...
G-protein-coupled inwardly rectifying potassium channel. HEK293A. human embryonic kidney cell line 293A. HPLC. high-performance ... HEK293A cells stably expressing G-protein-coupled inwardly rectifying potassium channels (HEK293A-GIRK) and the individual ... Plasma Protein Binding and Nonspecific Binding in Brain Homogenate. The extent of plasma protein binding and nonspecific ... Coupled with an unbound brain fraction (fu) of 0.011 for M1, the CNS distribution of the primary oxidative metabolite (M1) far ...
... aripiprazole antagonizes D2 receptor-mediated G-protein-coupled inwardly rectifying potassium channels and guanosine ... Bifeprunox is a partial agonist of the D2 dopamine receptor, a G-protein coupled receptor (GPCR). Like aripiprazole (Abilify), ... mitogen-activated protein kinase (MAPK) phosphorylation, potentiation of arachidonic acid (AA) release, and D2 receptor ...
G protein-coupled inwardly-rectifying potassium channel Inward-rectifier potassium ion channel GRCh38: Ensembl release 89: ... "A recombinant inwardly rectifying potassium channel coupled to GTP-binding proteins". The Journal of General Physiology. 107 (3 ... "G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase". The ... "Diverse trafficking patterns due to multiple traffic motifs in G protein-activated inwardly rectifying potassium channels from ...
G-Protein-Coupled Inwardly Rectifying Potassium (GIRK) Channel Activation by the p75 Neurotrophin Receptor Is Required for ... IK1 channels do not contribute to the slow afterhyperpolarization in pyramidal neurons. ...
GIRK2 is a member of G protein-coupled inwardly rectifying potassium channel family proteins (GIRKs). GIRK family proteins ... are related to yeast Hda1-like proteins, and class III proteins are related to the yeast protein Sir2. Inhibitors of HDAC ... including protein-protein interactions (4-6), regulation of GTP-binding protein function (7-9), DNA-associated activities (10, ... MEP50 is a WD repeat protein that may provide an interface for multiple protein interactions between methylosome proteins. (1 ...
G-protein coupled receptors that inhibit cAMP production and activate G-protein mediated inwardly rectifying potassium channels ... The size of plasma protein-binding is unknown but it could be similar to semi-synthetic opiates such as hydromorphone, about 19 ... proteins in the nucleus accumbens, thus indicating that these drugs cause their effects through signal transduction pathways ...
G Protein-Coupled Inwardly-Rectifying Potassium Channels / metabolism. Intracellular Signaling Peptides and Proteins / ... 0/G Protein-Coupled Inwardly-Rectifying Potassium Channels; 0/Intracellular Signaling Peptides and Proteins; 0/Neuropeptides; 0 ... it hyperpolarized the neurons by activating G-protein-gated inwardly rectifying potassium (GIRK) channels. Since concentrations ... 3A, baclofen triggered an inwardly rectifying current (n = 4), thereby suggesting that in CC, GIRK channels are still available ...
Multiple galanin receptors are predicted to mediate its effects, but only two functionally coupled receptors have been reported ... co-expressed with potassium channel subunits GIRK1 and GIRK4 resulted in inward K+ currents characteristic of Gi/Go-coupled ... Pharmacology and Activation of G-protein Inwardly Rectifying K+ Channels K E Smith 1 , M W Walker, R Artymyshyn, J Bard, B ... Pharmacology and Activation of G-protein Inwardly Rectifying K+ Channels K E Smith et al. J Biol Chem. 1998 ...
Differential Glycosylation of the Inwardly Rectifying Potassium Channel Kir7.1 by G protein-coupled Receptors. Molecular ... Ca2+/calmodulin-dependent protein kinase II regulates cardiac l-type Ca2+ channels via the beta subunit. Molecular Physiology ... Dopamine depletion alters the balance between CA2+/calmodulin-dependent protein kinase II and protein phosphatase I. Molecular ... Cholesteryl Ester Transfer Protein Modulates Liver Sex Hormone Signaling to Alter Triglyceride Metabolism in Male and Female ...
G-protein coupled inwardly rectifying potassium (GIRK) channels are effectors determining degree of analgesia experienced upon ... Future work should confirm these observations at the protein level to better understand how changes in VEGF transcription and ... Genetic interactions found between calcium channel genes modulate amyloid load measured by positron emission tomography. Human ... Both genes encode calcium channels expressed in the brain. The results shown here support previous animal studies implicating ...
... and P/Q-type calcium channels and activate inwardly rectifying potassium channels.[4][11] CB1 antagonists produce inverse ... CB1 receptors are coupled through Gi/o proteins and inhibit adenylyl cyclase and activate mitogen-activated protein (MAP) ... Both receptors are 7-transmembrane G-protein coupled receptors (GPCRs) which inhibit the accumulation of cyclic adenosine ...
... receptor agonists involves coordinated postsynaptic inhibition via G protein-coupled inwardly rectifying potassium channels ( ... Here, we used mice lacking the GIRK2 channel subunit to assess the relative contribution of these two effector systems to ... In addition, deletion of GIRK2 channels in mutant mice largely eliminated clonidine antinociception and significantly decreased ... our results suggest that the reduced pain responsiveness of male compared with female mice results in part from GIRK2-coupled ...
G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action. Nat. Neurosci. 2:1084-1090. doi:10.1038 ... Synergistic activation of G protein-gated inwardly rectifying potassium channels by the βγ subunits of G proteins and Na(+) and ... G protein-gated inwardly rectifying potassium (GIRK or Kir3) channels are expressed in various regions of the brain, where they ... G protein-gated inwardly rectifying potassium (GIRK) channels control neuronal excitability in the brain and are implicated in ...
2001a) Potassium channels as targets for ethanol: studies of G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2) ... 1997) G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in ... 2002) Diverse trafficking patterns due to multiple traffic motifs in G protein-activated inwardly rectifying potassium channels ... 1996) Heteromultimerization of G-protein-gated inwardly rectifying K+ channel proteins GIRK1 and GIRK2 and their altered ...
  • In response to Rho, mDia/diap proteins are involved in the regulation of multiple cell functions including cytoskeletal dynamics, migration, adhesion, polarity and cell shape (reviewed in 1,2).mDia1/diap1 is activated by GTP-bound Rho, leading to Rho-associated kinase (ROCK)-dependent stress fiber formation (3,4). (cellsignal.com)
  • Background: AMP-activated protein kinase (AMPK) is highly conserved from yeast to plants and animals and plays a key role in the regulation of energy homeostasis (1). (cellsignal.com)
  • These data confirm the functional efficacy of GALR3 receptors and further suggest that GALR3 signaling pathways resemble those of GALR1 in that both can activate potassium channels linked to the regulation of neurotransmitter release. (nih.gov)
  • Furthermore, the interaction domains include residues responsible for functional channel assembly ( 3 ), and for regulation by ATP ( 5 ), protons ( 6 ), and phospholipids ( 7 ). (diabetesjournals.org)
  • The endoplasmic reticulum (ER) plays a pivotal role in syntheses of proteins and steroid hormones and regulation of intracellular Ca2+ level. (bvsalud.org)
  • Furthermore, amphetamine-induced D2Rs dimerization may be associated with the D2R-DAT protein-protein interaction as an interfering peptide that disrupts the D2R-DAT coupling, blocked amphetamine-induced up-regulation of D2Rs dimerization. (biomedcentral.com)
  • Molecular mechanism of inward rectifier potassium channel 2.3 regulation by tax-interacting protein-1. (genes2cognition.org)
  • Tselnick ﻽ ﻽ er IF, Tsemakhovich V, Rishal I, Kahanovitch U, Dessauer CW , Dascal N. (2014) Dual regulation of G proteins and the G-protein-activated K+ channels by lithium . (dessauer-lab.com)
  • The current study examined the D2L receptor binding properties of aripiprazole, as well as the effects of the drug on three downstream D2 receptor-mediated functional effectors: mitogen-activated protein kinase (MAPK) phosphorylation, potentiation of arachidonic acid (AA) release, and D2 receptor internalization. (scienceblogs.com)
  • In addition, 2'-amino-3'-methoxyflavone (PD98059), an inhibitor of mitogen-activated protein (MAP) kinase kinase (MEK), had no effect on the m1 receptor-induced inhibition of Kir2.1, suggesting that MAP kinases are not involved in the signaling pathway. (uky.edu)
  • Interaction of the C-terminal tail region of the metabotropic glutamate receptor 7 with the protein kinase C substrate PICK 1. (mpg.de)
  • Although a large body of studies thus far failed to unravel the entire cellular signaling pathways that lead to preconditioning, it became clear that adenosine triphosphate-sensitive K + (K ATP ) channels can play a critical role in the process. (asahq.org)
  • Reflecting the increased amino acid transport capacity of tumor cells, F-18 fluroethyltyrosine (F-18 FET) is actively taken up in tumor cells via amino acid transport system L, but is neither incorporated into proteins nor readily degraded, resulting in high intracellular concentrations of this imaging agent. (cancer.gov)
  • The resulting potassium channel is sensitive to intracellular nucleotides, phospholipids, and several kinds of therapeutically important drugs, including sulfonylureas and potassium channel openers. (diabetesjournals.org)
  • A novel intracellular traffic coordinator pulls potassium channels from their job and whisks them to the recycling plant when not needed to put a damper on brain cells excitability, they report in the September issue of Nature Neuroscience. (bio-medicine.org)
  • Tax-interacting protein-1 (TIP-1), an atypical PDZ-domain-containing protein, binds to Kir2.3 with a high affinity, causing the intracellular accumulation of Kir2.3 in cultured epithelial cells. (genes2cognition.org)
  • Interestingly, the strength of the PIP 2 interaction with the channel can determine the level of basal channel activity, which varies considerably among different inward rectifiers. (rupress.org)
  • G proteins , also known as guanine nucleotide-binding proteins , are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. (wikipedia.org)
  • Atomistic molecular dynamic simulations of neuronal GIRK2 with the same 6′ substitution reveal an open GIRK2 channel with PIP 2 molecules adopting novel positions. (rupress.org)
  • With state-of-the art molecular biology and protein biochemistry labs, we work with our clients to rapidly evaluate in parallel to identify the optimal expression system for candidate proteins. (abgent.com)
  • Pubmed ID: 11801724 Mutations in the genes encoding the inner nuclear membrane proteins lamin A/C and emerin produce cardiomyopathy and muscular dystrophy in humans and mice. (jove.com)
  • Work during this time his work focused on the biophysical properties and modulation of neuronal voltage-gated ion channels. (nih.gov)
  • IRK channels possess a pore domain, homologous to that of voltage-gated ion channels , and flanking transmembrane segments (TMSs). (wikipedia.org)
  • COPII formation is initiated through the binding of the activated G protein, Sar1, to the Sec23/24 complex, thereby forming a prebudding complex that directly binds target molecules (1-3). (cellsignal.com)
  • It binds directly to cargo proteins at the ER and brings them to COPII vesicles through interaction with Sec23. (cellsignal.com)
  • The monoclonal antibody portion of the F16-IL2 fusion protein binds to tumor cells expressing the tumor associated antigen (TAA) tenascin-C. In turn, the IL-2 moiety of the fusion protein stimulates natural killer (NK) cells, macrophages and neutrophils and induces T-cell antitumor cellular immune responses thereby selectively killing tenascin-C-expressing tumor cells. (cancer.gov)
  • The antagonist 3-quinuclidinyl-benzilate binds in the middle of a long aqueous channel extending approximately two-thirds through the membrane. (sigmaaldrich.com)
  • ADPR binds to the NUDT9-H domain and, in the presence of Ca 2+ , gates channel opening ( Csanády and Törocsik, 2009 ). (rupress.org)
  • Selective enhancement of GIRK2 function by intoxicating concentrations of ethanol was recently shown for recombinant homomeric and heteromeric channels. (aspetjournals.org)