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.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 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, Inwardly Rectifying: Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.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.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.Kv1.3 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.Kv1.2 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.Kv1.1 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.Potassium Channels, Calcium-Activated: Potassium channels whose activation is dependent on intracellular calcium concentrations.Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.Shaw Potassium Channels: A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.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.KCNQ1 Potassium Channel: A voltage-gated potassium channel that is expressed primarily in the HEART.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.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.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.Kv1.4 Potassium Channel: A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.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).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.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).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.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.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.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.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.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.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.Tetraethylammonium: A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)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.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.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.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.G Protein-Coupled Inwardly-Rectifying Potassium Channels: A family of inwardly-rectifying potassium channels that are activated by PERTUSSIS TOXIN sensitive G-PROTEIN-COUPLED RECEPTORS. GIRK potassium channels are primarily activated by the complex of GTP-BINDING PROTEIN BETA SUBUNITS and GTP-BINDING PROTEIN GAMMA SUBUNITS.Small-Conductance Calcium-Activated Potassium Channels: A major class of calcium-activated potassium channels that are found primarily in excitable CELLS. They play important roles in the transmission of ACTION POTENTIALS and generate a long-lasting hyperpolarization known as the slow afterhyperpolarization.Chloride Channels: Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.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.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.Charybdotoxin: A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.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.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.Kinetics: The rate dynamics in chemical or physical systems.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.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.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.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.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.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)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.Potassium, Dietary: Potassium or potassium compounds used in foods or as foods.Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.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.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Tetraethylammonium CompoundsSulfonylurea 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.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.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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.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.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)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.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.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).Barium Compounds: Inorganic compounds that contain barium as an integral part of the molecule.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.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)Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.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.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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.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.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.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.Benzopyrans: Compounds with a core of fused benzo-pyran rings.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Apamin: A highly neurotoxic polypeptide from the venom of the honey bee (Apis mellifera). It consists of 18 amino acids with two disulfide bridges and causes hyperexcitability resulting in convulsions and respiratory paralysis.Large-Conductance Calcium-Activated Potassium Channel beta Subunits: The regulatory subunits of large-conductance calcium-activated potassium channels.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.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.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.Biophysics: The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.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.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.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.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.Acid Sensing Ion Channels: A family of proton-gated sodium channels that are primarily expressed in neuronal tissue. They are AMILORIDE-sensitive and are implicated in the signaling of a variety of neurological stimuli, most notably that of pain in response to acidic conditions.Epithelial Sodium Channels: Sodium channels found on salt-reabsorbing EPITHELIAL CELLS that line the distal NEPHRON; the distal COLON; SALIVARY DUCTS; SWEAT GLANDS; and the LUNG. They are AMILORIDE-sensitive and play a critical role in the control of sodium balance, BLOOD VOLUME, and BLOOD PRESSURE.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.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.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Diazoxide: A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.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.Biophysical Phenomena: The physical characteristics and processes of biological systems.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.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.Decanoic Acids: 10-carbon saturated monocarboxylic acids.Hydroxy Acids: Organic compounds containing both the hydroxyl and carboxyl radicals.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.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.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)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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.Kv1.6 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that has been described in NEURONS and ASTROCYTES.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Potassium Radioisotopes: Unstable isotopes of potassium that decay or disintegrate emitting radiation. K atoms with atomic weights 37, 38, 40, and 42-45 are radioactive potassium isotopes.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)Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.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.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Chlorides: Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.PhenylenediaminesRNA, 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.Cations: Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.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.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.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.Kv Channel-Interacting Proteins: A family of neuronal calcium-sensor proteins that interact with and regulate potassium channels, type A.Scyphozoa: The class of true jellyfish, in the phylum CNIDARIA. They are mostly free-swimming marine organisms that go through five stages in their life cycle and exhibit two body forms: polyp and medusa.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.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.DNA, 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.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.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.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.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Conotoxins: Peptide neurotoxins from the marine fish-hunting snails of the genus CONUS. They contain 13 to 29 amino acids which are strongly basic and are highly cross-linked by disulfide bonds. There are three types of conotoxins, omega-, alpha-, and mu-. OMEGA-CONOTOXINS inhibit voltage-activated entry of calcium into the presynaptic membrane and therefore the release of ACETYLCHOLINE. Alpha-conotoxins inhibit the postsynaptic acetylcholine receptor. Mu-conotoxins prevent the generation of muscle action potentials. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)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.Multigene Family: A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Aminopyridines: Pyridines substituted in any position with an amino group. May be hydrogenated, but must retain at least one double bond.Cation Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of positively charged molecules (cations) across a biological membrane.Calcium Channels, P-Type: CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.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).)Picolines: A group of compounds that are monomethyl derivatives of pyridines. (From Dorland, 28th ed)Minoxidil: A potent direct-acting peripheral vasodilator (VASODILATOR AGENTS) that reduces peripheral resistance and produces a fall in BLOOD PRESSURE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p371)Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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.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.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.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.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.Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.Nerve Tissue ProteinsHypokalemia: 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)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)Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.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.Heart: The hollow, muscular organ that maintains the circulation of the blood.Static Electricity: The accumulation of an electric charge on a objectNeurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.Quinidine: An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.NAV1.5 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of CARDIOMYOCYTES. Defects in the SCN5A gene, which codes for the alpha subunit of this sodium channel, are associated with a variety of CARDIAC DISEASES that result from loss of sodium channel function.Calcium Channels, Q-Type: CALCIUM CHANNELS located in the neurons of the brain.Anti-Arrhythmia Agents: Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Tolbutamide: A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.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.Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.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.Electrophysiological Phenomena: The electrical properties, characteristics of living organisms, and the processes of organisms or their parts that are involved in generating and responding to electrical charges.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.Mollusk Venoms: Venoms from mollusks, including CONUS and OCTOPUS species. The venoms contain proteins, enzymes, choline derivatives, slow-reacting substances, and several characterized polypeptide toxins that affect the nervous system. Mollusk venoms include cephalotoxin, venerupin, maculotoxin, surugatoxin, conotoxins, and murexine.Permeability: Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)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)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.Muscles: Contractile tissue that produces movement in animals.Mice, Neurologic Mutants: Mice which carry mutant genes for neurologic defects or abnormalities.Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to CADMIUM POISONING.Protein Structure, Quaternary: The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).Bacterial Proteins: Proteins found in any species of bacterium.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or 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.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.

Mutations in the S4 region isolate the final voltage-dependent cooperative step in potassium channel activation. (1/462)

Charged residues in the S4 transmembrane segment play a key role in determining the sensitivity of voltage-gated ion channels to changes in voltage across the cell membrane. However, cooperative interactions between subunits also affect the voltage dependence of channel opening, and these interactions can be altered by making substitutions at uncharged residues in the S4 region. We have studied the activation of two mutant Shaker channels that have different S4 amino acid sequences, ILT (V369I, I372L, and S376T) and Shaw S4 (the S4 of Drosophila Shaw substituted into Shaker), and yet have very similar ionic current properties. Both mutations affect cooperativity, making a cooperative transition in the activation pathway rate limiting and shifting it to very positive voltages, but analysis of gating and ionic current recordings reveals that the ILT and Shaw S4 mutant channels have different activation pathways. Analysis of gating currents suggests that the dominant effect of the ILT mutation is to make the final cooperative transition to the open state of the channel rate limiting in an activation pathway that otherwise resembles that of Shaker. The charge movement associated with the final gating transition in ILT activation can be measured as an isolated component of charge movement in the voltage range of channel opening and accounts for 13% ( approximately 1.8 e0) of the total charge moved in the ILT activation pathway. The remainder of the ILT gating charge (87%) moves at negative voltages, where channels do not open, and confirms the presence of Shaker-like conformational changes between closed states in the activation pathway. In contrast to ILT, the activation pathway of Shaw S4 seems to involve a single cooperative charge-moving step between a closed and an open state. We cannot detect any voltage-dependent transitions between closed states for Shaw S4. Restoring basic residues that are missing in Shaw S4 (R1, R2, and K7) rescues charge movement between closed states in the activation pathway, but does not alter the voltage dependence of the rate-limiting transition in activation.  (+info)

Helical structure and packing orientation of the S2 segment in the Shaker K+ channel. (2/462)

Six transmembrane segments, S1-S6, cluster around the central pore-forming region in voltage-gated K+ channels. To investigate the structural characteristics of the S2 segment in the Shaker K+ channel, we replaced each residue in S2 singly with tryptophan (or with alanine for the native tryptophan). All but one of the 23 Trp mutants expressed voltage-dependent K+ currents in Xenopus oocytes. The effects of the mutations were classified as being of low or high impact on channel gating properties. The periodicity evident in the effects of these mutations supports an alpha-helical structure for the S2 segment. The high- and low-impact residues cluster onto opposite faces of a helical wheel projection of the S2 segment. The low-impact face is also tolerant of single mutations to asparagine. All results are consistent with the idea that the low-impact face projects toward membrane lipids and that changes in S2 packing occur upon channel opening. We conclude that the S2 segment is a transmembrane alpha helix and that the high-impact face packs against other transmembrane segments in the functional channel.  (+info)

Overexpression of a Shaker-type potassium channel in mammalian central nervous system dysregulates native potassium channel gene expression. (3/462)

The nervous system maintains a delicate balance between excitation and inhibition, partly through the complex interplay between voltage-gated sodium and potassium ion channels. Because K+ channel blockade or gene deletion causes hyperexcitability, it is generally assumed that increases in K+ channel gene expression should reduce neuronal network excitability. We have tested this hypothesis by creating a transgenic mouse that expresses a Shaker-type K+ channel gene. Paradoxically, we find that addition of the extra K+ channel gene results in a hyperexcitable rather than a hypoexcitable phenotype. The presence of the transgene leads to a complex deregulation of endogenous Shaker genes in the adult central nervous system as well as an increase in network excitability that includes spontaneous cortical spike and wave discharges and a lower threshold for epileptiform bursting in isolated hippocampal slices. These data suggest that an increase in K+ channel gene dosage leads to dysregulation of normal K+ channel gene expression, and it may underlie a mechanism contributing to the pathogenesis of human aneuploidies such as Down syndrome.  (+info)

Molecular modeling of voltage-gated potassium channel pore. (4/462)

AIM: To build a structure model for the pore of voltage-gated Shaker potassium channel and examine its validity. METHODS: (1) Structural restraints were derived from experimental and theoretical studies; (2) An initial structural motif satisfying the derived restraints was first constructed, and further refined by restrained molecular mechanics; (3) The quality of the model was judged by the criterion that whether it could clarify molecular mechanisms of channel functions and explain the known experimental facts. RESULTS: (1) A computer pore structure was proposed, in which the residues within signature sequence (corresponding to Shaker 439-446) dipped into the membrane and formed the narrow part of the pore in a non-periodic conformation, while the other residues in the P region constituted the outer mouth of the pore; (2) The ion selectivity was achieved through cation-pi orbital interaction mechanism at position 445 and oxygen cage mechanism at position 447; (3) Different binding modes led to different affinity of CTX and AgTx2 to channel; and (4) The inside of pore was dominated by negative electrostatic potential. CONCLUSION: The model proposed was consistent with the derived restraints from the experimental results.  (+info)

IA in Kenyon cells of the mushroom body of honeybees resembles shaker currents: kinetics, modulation by K+, and simulation. (5/462)

Cultured Kenyon cells from the mushroom body of the honeybee, Apis mellifera, show a voltage-gated, fast transient K+ current that is sensitive to 4-aminopyridine, an A current. The kinetic properties of this A current and its modulation by extracellular K+ ions were investigated in vitro with the whole cell patch-clamp technique. The A current was isolated from other voltage-gated currents either pharmacologically or with suitable voltage-clamp protocols. Hodgkin- and Huxley-style mathematical equations were used for the description of this current and for the simulation of action potentials in a Kenyon cell model. Activation and inactivation of the A current are fast and voltage dependent with time constants of 0.4 +/- 0.1 ms (means +/- SE) at +45 mV and 3.0 +/- 1.6 ms at +45 mV, respectively. The pronounced voltage dependence of the inactivation kinetics indicates that at least a part of this current of the honeybee Kenyon cells is a shaker-like current. Deactivation and recovery from inactivation also show voltage dependency. The time constant of deactivation has a value of 0.4 +/- 0.1 ms at -75 mV. Recovery from inactivation needs a double-exponential function to be fitted adequately; the resulting time constants are 18 +/- 3.1 ms for the fast and 745 +/- 107 ms for the slow process at -75 mV. Half-maximal activation of the A current occurs at -0.7 +/- 2.9 mV, and half-maximal inactivation occurs at -54.7 +/- 2.4 mV. An increase in the extracellular K+ concentration increases the conductance and accelerates the recovery from inactivation of the A current, affecting the slow but not the fast time constant. With respect to these modulations the current under investigation resembles some of the shaker-like currents. The data of the A current were incorporated into a reduced computational model of the voltage-gated currents of Kenyon cells. In addition, the model contained a delayed rectifier K+ current, a Na+ current, and a leakage current. The model is able to generate an action potential on current injection. The model predicts that the A current causes repolarization of the action potential but not a delay in the initiation of the action potential. It further predicts that the activation of the delayed rectifier K+ current is too slow to contribute markedly to repolarization during a single action potential. Because of its fast activation, the A current reduces the amplitude of the net depolarizing current and thus reduces the peak amplitude and the duration of the action potential.  (+info)

The effects of level of expression of a jellyfish Shaker potassium channel: a positive potassium feedback mechanism. (6/462)

1. When jellyfish Shaker potassium channels (jShak2) are heterologously expressed in Xenopus oocytes at different levels they demonstrate density-dependent changes in electrical and kinetic properties of macroscopic currents. 2. The activation and inactivation properties of jShak2 channels depend on the extracellular potassium concentration. In this study we present experimental data which show that expression-dependent changes in kinetic and electrical properties of jShak2 macroscopic currents can be explained by the positive feedback effect of dynamic accumulation of K+ in the perimembranal space.  (+info)

Auxiliary Hyperkinetic beta subunit of K+ channels: regulation of firing properties and K+ currents in Drosophila neurons. (7/462)

Auxiliary Hyperkinetic beta subunit of K+ channels: regulation of firing properties and K+ currents in Drosophila neurons. Molecular analysis and heterologous expression have shown that K+ channel beta subunits regulate the properties of the pore-forming alpha subunits, although how they influence neuronal K+ currents and excitability remains to be explored. We studied cultured Drosophila "giant" neurons derived from mutants of the Hyperkinetic (Hk) gene, which codes for a K+ channel beta subunit. Whole cell patch-clamp recording revealed broadened action potentials and, more strikingly, persistent rhythmic spontaneous activities in a portion of mutant neurons. Voltage-clamp analysis demonstrated extensive alterations in the kinetics and voltage dependence of K+ current activation and inactivation, especially at subthreshold membrane potentials, suggesting a role in regulating the quiescent state of neurons that are capable of tonic firing. Altered sensitivity of Hk currents to classical K+ channel blockers (4-aminopyridine, alpha-dendrotoxin, and TEA) indicated that Hk mutations modify interactions between voltage-activated K+ channels and these pharmacological probes, apparently by changing both the intra- and extracellular regions of the channel pore. Correlation of voltage- and current-clamp data from the same cells indicated that Hk mutations affect not only the persistently active neurons, but also other neuronal categories. Shaker (Sh) mutations, which alter K+ channel alpha subunits, increased neuronal excitability but did not cause the robust spontaneous activity characteristic of some Hk neurons. Significantly, Hk Sh double mutants were indistinguishable from Sh single mutants, implying that the rhythmic Hk firing pattern is conferred by intact Shalpha subunits in a distinct neuronal subpopulation. Our results suggest that alterations in beta subunit regulation, rather than elimination or addition of alpha subunits, may cause striking modifications in the excitability state of neurons, which may be important for complex neuronal function and plasticity.  (+info)

Peptidyl inhibitors of shaker-type Kv1 channels elicit twitches in guinea pig ileum by blocking kv1.1 at enteric nervous system and enhancing acetylcholine release. (8/462)

Potent and selective peptidyl blockers of the Shaker-type (Kv1) voltage-gated potassium channels were used to determine the role of these channels in regulating the spontaneous motility of smooth muscle preparations. Margatoxin (MgTX), kaliotoxin, and agitoxin-2 at 1 to 10 nM and agitoxin-1 at 50 to 100 nM induce twitches in guinea pig ileum strips. These twitches are abolished by tetrodotoxin (TTX, 0.5 microM), atropine (1 microM), hexamethonium (10 microM), or nifedipine (0.1 microM). It is proposed that blockade of Kv1 channels by MgTX, kaliotoxin, or the agitoxins increases excitability of intramural nerve plexuses in the ileum, promoting release of acetylcholine from excitatory motor nerve terminals. This, in turn, leads to Ca2+-dependent action potentials and twitching of the muscle fibers. MgTX does not induce twitches in several other guinea pig and/or rat vascular, genitourinary, or gastrointestinal smooth muscles, although small increases in spontaneous myogenic activity may be seen in detrusor muscle exposed to >30 nM MgTX. This effect is not reversed by TTX or atropine. The TTX- and atropine-sensitive twitches of guinea pig ileum are also induced by nanomolar concentrations of alpha-dendrotoxin, a selective blocker of Shaker Kv1.1 and 1.2 subtypes, or stichodactylatoxin, a peptide isolated from sea anemone that displays high affinity for Kv1.1 and 1.3, but not by charybdotoxin, which blocks Kv1.2 and 1.3 but not 1.1. The data taken together suggest that high-affinity blockade of Kv1.1 underlies the ability of MgTX, kaliotoxin, agitoxin-1, agitoxin-2, alpha-dendrotoxin, and stichodactylatoxin to elicit TTX-sensitive twitches in guinea pig ileum.  (+info)

In this paper, we investigated the interaction of hanatoxin with the Shaker Kv channel. In contrast to the inhibitory actions of the toxin on Kv2.1 channels investigated in previous studies (Swartz and MacKinnon, 1997a,b; Li-Smerin and Swartz, 1998, 2000, 2001; Lee et al., 2003; Wang et al., 2004; Phillips et al., 2005; Alabi et al., 2007; Bosmans et al., 2008), our results show that hanatoxin facilitates opening of the Shaker Kv channel by interacting with the paddle motif (Figs. 1-3), stabilizing the voltage sensor in the activated state (Fig. 5), and influencing the final opening transition to stabilize the open state of the pore (Figs. 4 and 6). Although the effects of hanatoxin on the G-V relations (Figs. 1 and 2), the kinetics of channel closure (Figs. 1 and 4), and the ILT channel (Fig. 6) could in part be explained by effects on the final opening transition in Shaker, the pronounced effects of the toxin on gating currents (Fig. 5) suggest that early transitions in the voltage sensors are ...
Backbench Business. Shaker Aamer. John McDonnell (Hayes and Harlington) (Lab): I beg to move, "That this House calls on the US Government to release Shaker Aamer from his imprisonment in Guantánamo Bay and to allow him to return to his family in the UK.". I thank the Backbench Business Committee for allocating time for this critical debate at an important time in the campaign to secure the release of Shaker Aamer. By way of introduction, I pay tribute to all those who have campaigned so hard over many years to bring Shaker Aamers case to our attention. I pay tribute to the "Save Shaker Aamer Campaign", and all those campaigners who have stood in Parliament Square month after month protesting in their orange boiler suits with their placards until someone began to listen to them. I pay tribute to the "We Stand with Shaker" campaign, to Shakers family who have joined us today and to the organisations Reprieve and Amnesty International. I pay tribute, too, to the full range of newspapers that ...
Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. It plays an essential role in T-cell proliferation and activation. This gene appears to be intronless and it is clustered together with KCNA2 and KCNA10 genes on chromosome 1.
1989 by the National Academy of Sciences. Contributed by N. Davidson, July 14, 1989. We thank Barbara Thorne for expert assistance in the construction of the recombinant virus and J.H. Strauss and R.W. Aldrich for advice. Charybdotoxin was a generous gift of Dr. M.L. Garcia (Merck Sharp & Dohme Research Laboratories). This work was supported by National Institutes of Health Grants GM10991, GM29836, and DK37274, by the Cystic Fibrosis Foundation, and by fellowships from the Max Kade Foundation (A.K.) and the National Institutes of Health (R.J.L.). The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact ...
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The equilibrium of voltage sensors between resting and activated states, as reflected in the gating charge (Q) versus voltage (V) relation, is sensitive to the initial voltage from which gating currents are elicited. For example, in a variety of voltage-activated channels and the Ci-VSP voltage-sensitive phosphatase, Q-V relations exhibit a pronounced shift to negative voltages when gating currents are elicited from positive voltages (Bezanilla et al., 1982; Olcese et al., 1997; Villalba-Galea et al., 2008). Villalba-Galea et al. (2008) have proposed that prolonged activation of voltage sensors at positive voltages causes them to shift into a relaxed state, and that the crystal structures of Kv channels represent this relaxed state rather than the activated state. Our constraints with bridges between S4 in both pre-open and open states are compatible with the crystal structure of the Kv1.2 paddle chimera, as discussed above, suggesting that the structural differences between activated and ...
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CHARLES MINER, a well known member of the North Family Shakers, Enfield, N. H. committed suicide sometime during Monday night, on May 1st, shooting himself through the head with a small rifle, in his room, at Shaker Village. He was about 62 years of age. This Spring he had charge of the sugar camp and to the many who visited him there, [he] seemed to be social and happy, but at other times he has shown signs of being a little "out." Lately he talked of leaving the Shakers, and only the P.M. before he shot himself, he was over in the village at North Enfield, endeavoring to obtain employ. His dead body was discovered in his room, on Tuesday morning, the rifle by his side. ...
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Kv1.2 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.
Kv1.1 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.
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Phosphatidic acid influences the gating of voltage-gated K+ channels through a non-specific surface charge mechanism and through a specific interaction between a voltage sensor arginine and the primary phosphate head group on the cytoplasmic membrane leaflet.
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Ahojky, tak ja sa pripojim :) Ja mam rovnakeho priatela ako Ty - v urcitom smere. On sice za mnou chodi pravidelne, sme spolu ale uz par rokov, ale nebolo to vzdy rovnake - najskor sme sa spolu stretavali vonku, potom chodil on za mnou a ja k nemu este nie, pak ja k nemu viackrat za tyzden a on menej krat za mnou, teraz zasa chodi viacmenej on ku mne a spolocne id. k nim k jeho rod. na navstevu, proste ako nam to vyhovuje kvoli ostatnym veciam - praci a podobne. Zalezi, ako ste spolu dlho. My v tomto problem nemame, skor je problem v tom, ze on aj podla znamenia na nom sedi, ze je skor taky domased a ja skor spolocenska.. tak skor bol problem, ako travit vikend, ked mame volno. Zo zaciatku sme samozrejme spolu podnikali vela veci, casom sa to otupilo, uz si bol asi mnou isty :-), tak sa nesnazil az tak - pretoze to nie je jeho prirodzena stranka.. No a tu som nastupila ja - kdezto on to neprijimal moc pozitivne moje navrhy chodit niekam von (do prirody, na vylety a pod.), takze sme vsetko ...
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AbstrakPerubahan gambaran elektrokardiogram (EKG) terjadi pada fase akut IMA EST baik berupa perubahan repolarisasi ataupun perubahan depolarisasi. Skor QRS Selvester dan pemanjangan kompleks QRS merupakan parameter yang digunakan untuk memperkirakan luas infark dan penilaian iskemia. Tujuan penulisan ini adalah untuk mengetahui mekanisme perubahan durasi QRS dan skor QRS Selvester setelah reperfusi yang optimal. Penulisan artikel ini berdasarkan studi kepustakaan yang terkait dengan peranan durasi QRS dan skor QRS Selvester serta keberhasilan reperfusi miokard. Iskemia mengakibatkan perubahan gambaran listrik sel miokard normal, sehingga terjadi perubahan gambaran EKG yaitu meliputi perubahan gelombang T, elevasi segmen ST dan distorsi dengan pemanjangan kompleks QRS. Penilaian luas infark dapat dilakukan dengan menilai skor QRS Selvester. Iskemia juga mengakibatkan pemanjangan kompleks QRS melalui pemanjangan konduksi purkinye dan blok peri-infark. Reperfusi optimal dapat mengakibatkan regresi ...
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Alignments were performed using ClustalW (http://www.genome.jp/tools/clustalw/) and BOXSHADE 3.21 (http://www.ch.embnet.org/software/BOX_form.html). A homology model of Arabidopsis TPC1 was derived from the crystal structure of a chimeric voltage-dependent K+ channel in which the voltage-sensor paddle had been transferred from Kv2.1 to Kv1.2 (Long et al., 2005, 2007). The 12 transmembrane helices of TPC1 were predicted from the amino acid sequence using the TMHMM Server. As TPC1 presents a dimeric assembly of two Shaker-like domains, the sequence of TPC1 was separated into the N- and C-terminal half (each comprising six predicted transmembrane helices, residues Ser-60 to Glu-310 and Pro-430 to Asp-680), and both halves were aligned to the sequences of the voltage paddle chimera of the mammalian voltage-dependent K+ channels Kv1.2 and Kv2.1 of the Shaker family (PDB entries 2R9R and 2A79). Manual editing was performed to shift insertions and deletions within the transmembrane helices to the loop ...
The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
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https://youtu.be/LiGavFvzhfg Aloha Guys! Today Im making a see through Acetate shaker card for Tupelo Designs LLC. This is fairly simple to make so I plan to mass produce this for gifts, by using all the different patterns on this Acetate pack. This is a 6x6 WRMC Acetate pad and for each design there are gold,…
Is your dogs breed susceptible to Shaker Syndrome? Find out how to treat it, what it costs, and whether pet insurance covers it.
Should you not wish to sacrifice the mate to a pair, lonely salt and pepper shakers are readily available at garage sales and thrift stores. On the other hand, if you have a cheapo set of shakers like these, maybe you do want to sacrifice them and upgrade- there are all kinds of interesting shakers out there, whether youre into bikes, Lego, carnivorism, architecture, bathroom humor, modern design, or chemistry.. Next, Im going to start looking for a parmesan shaker for our barbeque skewers.. ...
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... targets are Shaker-type (Kv1) K+ channels. HgTX1 shows high affinity with Kv1.1, Kv1.2, Kv1.3 voltage-gated potassium channels ... Hongotoxin belongs to the short scorpion toxin superfamily. Potassium channel inhibitor family. Alpha-KTx 2 subfamily. There ... Hongotoxin (HgTX) is an ion channel toxin, which blocks Shaker-type (Kv1) K+ channels. The toxin is derived from the venom of ... HgTX4 and HgTX5 are potent selective inhibitors of Kv1 voltage-gated potassium channels (By similarity). ND, not determined. ...
Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has ... McCormack T, McCormack K (1995). "Shaker K+ channel beta subunits belong to an NAD(P)H-dependent oxidoreductase superfamily". ... Voltage-gated potassium channel subunit beta-1 is a protein that in humans is encoded by the KCNAB1 gene. Potassium channels ... "Entrez Gene: KCNAB1 potassium voltage-gated channel, shaker-related subfamily, beta member 1". England SK, Uebele VN, Shear H, ...
These include the sodium, potassium, calcium, ryanodine receptor, HCN, CNG, CatSper, and TRP channels. This large group of ion ... Shaker-related: Kv1.4 (KCNA4) Kvα3.x - Shaw-related: Kv3.3 (KCNC3), Kv3.4 (KCNC4) Kvα4.x - Shal-related: Kv4.1 (KCND1), Kv4.2 ( ... The transmembrane cation channel superfamily was defined in InterPro and Pfam as the family of tetrameric ion channels. ... Durell SR, Guy HR (2001). "A family of putative Kir potassium channels in prokaryotes". BMC Evolutionary Biology. 1: 14. doi: ...
The primary targets consist of voltage-gated Shaker-related potassium channels, ether-a-go-go related gene (HERG) potassium ... TmTx belongs to the short scorpion toxin superfamily and the potassium channel inhibitor family. Adhering to the nomenclature ... calcium-activated potassium channel), respectively. Another suggested target is the Kv1.6 channel, a voltage-gated potassium ... It belongs to the group of alpha potassium toxins (α-KTx: alpha toxin affecting potassium channels). This group contains short- ...
"Multiple potassium-channel components are produced by alternative splicing at the Shaker locus in Drosophila". Nature. 331 ( ... K+ channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six ... channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+ channels; and three types of calcium (Ca)- ... Potassium channels are the most diverse group of the ion channel family. They are important in shaping the action potential, ...
Such genetic methods allowed the genetic identification of the "Shaker" K+ channel gene in Drosophila before ion channel gene ... at ualberta.ca UMich Orientation of Proteins in Membranes families/superfamily-8 - Spatial positions of voltage gated potassium ... preventing ion movement through the channel. Ion channel Potassium channel tetramerisation domain Ion channel family ... Voltage-gated potassium channels (VGKCs) are transmembrane channels specific for potassium and sensitive to voltage changes in ...
... of other important voltage conducting proteins such as the drosophilla-derived Shaker and the human hERG potassium channel. ... "Overview of molecular relationships in the voltage-gated ion channel superfamily". Pharmacological Reviews. 57 (4): 387-95. doi ... Calcium channel Potassium channel Sodium channel Schrempf H, Schmidt O, Kümmerlen R, Hinnah S, Müller D, Betzler M, Steinkamp T ... The KcsA channel is considered a model channel because the KcsA structure provides a framework for understanding K+ channel ...
... shaker superfamily of potassium channels MeSH D12.776.543.550.425.750.900.500.124 -- kv1.1 potassium channel MeSH D12.776. ... shaker superfamily of potassium channels MeSH D12.776.543.585.400.750.900.624.124 -- kv1.1 potassium channel MeSH D12.776. ... 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. ...
Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has ... McCormack T, McCormack K (1995). "Shaker K+ channel beta subunits belong to an NAD(P)H-dependent oxidoreductase superfamily". ... "Entrez Gene: KCNAB2 potassium voltage-gated channel, shaker-related subfamily, beta member 2". Hoek KS, Schlegel NC, Eichhoff ... Gu C, Jan YN, Jan LY (2003). "A conserved domain in axonal targeting of Kv1 (Shaker) voltage-gated potassium channels". Science ...
... shaker superfamily of potassium channels MeSH D12.776.157.530.400.600.900.500.124 -- kv1.1 potassium channel MeSH D12.776. ... shab potassium channels MeSH D12.776.157.530.400.600.900.249 -- ether-a-go-go potassium channels MeSH D12.776.157.530.400.600. ... kcnq potassium channels MeSH D12.776.157.530.400.600.900.124.249.500 -- kcnq1 potassium channel MeSH D12.776.157.530.400.600. ... kcnq2 potassium channel MeSH D12.776.157.530.400.600.900.124.249.875 -- kcnq3 potassium channel MeSH D12.776.157.530.400.600. ...
Potassium channels are the largest and most diverse class of voltage-gated channels, with over 100 encoding human genes. These ... Koishi R, Xu H, Ren D, Navarro B, Spiller BW, Shi Q, Clapham DE (March 2004). "A superfamily of voltage-gated sodium channels ... Webster SM, Del Camino D, Dekker JP, Yellen G (April 2004). "Intracellular gate opening in Shaker K+ channels defined by high- ... Voltage-gated ion-channels are usually ion-specific, and channels specific to sodium (Na+), potassium (K+), calcium (Ca2+), and ...
The potassium channels that hanatoxin inhibits have huge diversity and are involved in a number of functions such as regulation ... Gonzalez, C. e.a. (2000). "Modulation of the Shaker K(+) channel gating kinetics by the S3-S4 linker". Journal of General ... http://supfam.org/SUPERFAMILY/cgi-bin/search.cgi?search_field=hanatoxin, consulted 10th Oct. 2012. http://www.t3db.org/toxins, ... Swartz, K.J.; MacKinnon, R. (1995). "An Inhibitor of the Kv2.1 Potassium Channel Isolated from the Venom of a Chilean Tarantula ...
Choi KL, Mossman C, Aubé J, Yellen G (Mar 1993). "The internal quaternary ammonium receptor site of Shaker potassium channels ... UMich Orientation of Proteins in Membranes families/superfamily-8. ... Potassium channel blockers inhibit the flow of potassium ions through the channel. They either compete with potassium binding ... Proteopedia channel Potassium channel in 3D Potassium Channels at the US National Library of Medicine Medical Subject Headings ...
Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has ... a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ ... "Entrez Gene: KCNA2 potassium voltage-gated channel, shaker-related subfamily, member 2". Coleman SK, Newcombe J, Pryke J, Dolly ... Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural ...
Some potassium channels: Inward-rectifier potassium channels: These channels allow potassium ions to flow into the cell in an " ... Cyclic nucleotide-gated channels: This superfamily of channels contains two families: the cyclic nucleotide-gated (CNG) ... Shaker gene mutations cause a defect in the voltage gated ion channels, slowing down the repolarization of the cell. Equine ... Potassium channels Voltage-gated potassium channels e.g., Kvs, Kirs etc. Calcium-activated potassium channels e.g., BKCa or ...
In a few cases, those of Kir1.1a, Kir6.1 and Kir6.2, for example, direct interaction with a member of the ABC superfamily has ... Inward-rectifier potassium channels (Kir, IRK) are a specific subset of potassium channels. To date, seven subfamilies have ... such as the delayed rectifier and A-type potassium channels. Those more "typical" potassium channels preferentially carry ... "Inwardly Recifying Potassium Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and ...
... results in activation of calcium-sensitive potassium channels, muscular contraction,[4] excitation of neurons, up-regulation of ... High-voltage-gated calcium channels include the neural N-type channel blocked by ω-conotoxin GVIA, the R-type channel (R stands ... to at least 1 site on the channel, as Ca2+-null CaM mutants abolish CGI in L-type channels. Not all channels exhibit the same ... P-type calcium channel ("Purkinje") /Q-type calcium channel. HVA (high voltage activated). Cav2.1 (CACNA1A). α2δ, β, possibly γ ...
In a few cases, those of Kir1.1a, Kir6.1 and Kir6.2, for example, direct interaction with a member of the ABC superfamily has ... Inward-rectifier potassium channels (Kir, IRK) are a specific subset of potassium channels. To date, seven subfamilies have ... such as the delayed rectifier and A-type potassium channels. Those more "typical" potassium channels preferentially carry ... "Inwardly Recifying Potassium Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and ...
INVOLVED IN potassium ion transmembrane transport (ortholog); FOUND IN axon; axon terminus; integral component of plasma ... ENCODES a protein that exhibits delayed rectifier potassium channel activity (ortholog); ... Superfamily-SCOP. BTB/POZ_fold. UniProtKB/Swiss-Prot. UniGene. Mm.62535. ENTREZGENE. ... potassium voltage gated channel, shaker related, subfamily, member 6; potassium voltage-gated channel subfamily A member 6; ...
Shaker complex. In a first stage, a large number of models of the complex are generated using high temperature molecular ... Potassium Channels * Scorpion Venoms * Shaker Superfamily of Potassium Channels * Water * agitoxin 2 ... Modeling the Structure of Agitoxin in Complex With the Shaker K+ Channel: A Computational Approach Based on Experimental ... In this final complex, the toxin is bound to the extracellular entrance of the channel along the pore axis via a combination of ...
Potassium Channels, Voltage-Gated * Sh protein, Drosophila * Shaker Superfamily of Potassium Channels ... Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1 Nat Genet. 1994 ... Linkage studies in four such families suggested localization of an EA/myokymia gene near the voltage gated K+ channel gene, ... Potassium Channels / chemistry * Potassium Channels / deficiency * Potassium Channels / genetics* * Potassium Channels / ...
... the chromoionophore compounds further comprise a second chromophoric moiety which is insensitive to potassium binding by the ... Potassium channel subunits of the Shaker-like superfamily share a characteristic six transmembrane/1 pore domain structure. ... The Shaker-like channel family includes the voltage-gated potassium channels as well as the delayed rectifier type channels ... A second superfamily of potassium channels is composed of the inward rectifying channels (Kir). Kir channels have the property ...
Voltage-gated potassium channels (Kv) of the Shaker-related superfamily are assembled from membrane-integrated alpha subunits ... The beta subunits may increase Kv channel surface expression and/or confer A-type behavior to noninactivating Kv channels in ... Functional and molecular aspects of voltage-gated K+ channel beta subunits.. Pongs O1, Leicher T, Berger M, Roeper J, Bähring R ... Loss of function of Kv beta 1.1 subunits leads to a reduction of A-type Kv channel activity in hippocampal and striatal neurons ...
... targets are Shaker-type (Kv1) K+ channels. HgTX1 shows high affinity with Kv1.1, Kv1.2, Kv1.3 voltage-gated potassium channels ... Hongotoxin belongs to the short scorpion toxin superfamily. Potassium channel inhibitor family. Alpha-KTx 2 subfamily. There ... Hongotoxin (HgTX) is an ion channel toxin, which blocks Shaker-type (Kv1) K+ channels. The toxin is derived from the venom of ... HgTX4 and HgTX5 are potent selective inhibitors of Kv1 voltage-gated potassium channels (By similarity). ND, not determined. ...
Members of the superfamily of voltage-gated ion channels are the molecular components underlying electrical excitability in ... Luminescence Resonance Energy Transfer Studies of the Shaker Potassium Voltage-Gated Ion Channel. Welcome to the IDEALS ... Luminescence Resonance Energy Transfer Studies of the Shaker Potassium Voltage-Gated Ion Channel. Posson, David John ... Luminescence Resonance Energy Transfer Studies of the Shaker Potassium Voltage-Gated Ion Channel. ...
Kv4 channels may underlie the IA in DRG neurons. We combined electrophysiology, molecular biology (whole-tissue and single-cell ... Matching Kv4 channel properties, activation and inactivation of this IA occur in the subthreshold range of membrane potentials ... Contrasting the expression patterns of Kv4 channels in the central and peripheral nervous systems, we discuss possible ... Recent studies have demonstrated DRG hyperexcitability associated with downregulation of A-type K+ channels; however, the ...
Shaker Superfamily of Potassium Channels/*chemistry/*metabolism Identifiers. URN: urn:nbn:se:su:diva-18687ISI: 000246599900015 ... Contribution of hydrophobic and electrostatic interactions to the membrane integration of the Shaker K+ channel voltage sensor ...
These include the sodium, potassium, calcium, ryanodine receptor, HCN, CNG, CatSper, and TRP channels. This large group of ion ... Shaker-related: Kv1.4 (KCNA4) Kvα3.x - Shaw-related: Kv3.3 (KCNC3), Kv3.4 (KCNC4) Kvα4.x - Shal-related: Kv4.1 (KCND1), Kv4.2 ( ... The transmembrane cation channel superfamily was defined in InterPro and Pfam as the family of tetrameric ion channels. ... Durell SR, Guy HR (2001). "A family of putative Kir potassium channels in prokaryotes". BMC Evolutionary Biology. 1: 14. doi: ...
Shaker Superfamily of Potassium Channels Medicine & Life Sciences * Palinuridae Medicine & Life Sciences ... Expression of Panulirus shaker potassium channel splice variants. Receptors and Channels. 1998 Jul 31;5(5):291-304. ... title = "Expression of Panulirus shaker potassium channel splice variants",. abstract = "In Drosophila shaker voltage-dependent ... Expression of Panulirus shaker potassium channel splice variants. In: Receptors and Channels. 1998 ; Vol. 5, No. 5. pp. 291-304 ...
... that AKT1 and KAT1 are members of a family of plant channels similar in structure and sequence to the shaker superfamily of ... Among the several shaker-like channel genes identified in plants isAKT2 (Cao et al., 1995; Ketchum and Slayman, 1996), a K+ ... 2000) A shaker-like channel with weak rectification is expressed in both source and sink phloem tissues of Arabidopsis. Plant ... 1998b) Identification and disruption of a plant shaker-like outward channel involved in K+ release into the xylem sap. Cell 94: ...
... including the Shaker potassium channel (Kreusch et al., 1998) and, as an isolated domain, the Kv1.2 channel itself (Minor et al ... This superfamily includes members whose SCOP family is the "tetramerization domain of potassium channels." This structure, ... The assertions of the presence of the SCOP superfamilies "POZ domain" and "voltage-gated potassium channels" are the only two ... Crystal structure of the tetramerization domain of the Shaker potassium channel. Nature. 392:945-948. ...
Highly temperature-sensitive behavior of voltage-gated potassium channels provides a mechanistic model for how heat-activated ... TRP channels serve as temperature and pain sensors. ... Shaker ILT and Shaker V2 channels. For Shaker WT channel I2 was ... channels. As members of the tetrameric cation channel superfamily, TRP channels and Kv channels are structurally similar. They ... Activation of Shaker potassium channels. II. Kinetics of the V2 mutant channel * NE Schoppa ...
Expression of background potassium channels in rat DRG is cell-specific and down-regulated in a neuropathic pain model. Pollema ... Properties and functional role of voltage-dependent potassium channels in dendrites of rat cerebellar Purkinje neurons. Martina ... Voltage-dependent potassium currents during fast spikes of rat cerebellar Purkinje neurons: Inhibition by BDS-I toxin. Martina ... Acid-sensing ion channels contribute to chemosensitivity of breathing-related neurons of the nucleus of the solitary tract. ...
Shaker Superfamily of Potassium Channels Chromosomes, Human, Pair 3 Chromosomes, Human, Pair 1 ... N2 - The gating properties and current amplitudes of mammalian voltage- activated Shaker potassium channels are modulated by at ... AB - The gating properties and current amplitudes of mammalian voltage- activated Shaker potassium channels are modulated by at ... The gating properties and current amplitudes of mammalian voltage- activated Shaker potassium channels are modulated by at ...
Potassium Channels * Spectrum Analysis * Shaker Superfamily of Potassium Channels * Lanthanoid Series Elements ... Atomic scale movement of the voltage-sensing region in a potassium channel measured via spectroscopy. Cha, A., Snyder, G. E., ...
Recently, synthetic mutagenesis studies in the Drosophila melanogaster Shaker channel and analysis of human disease-causing ... highly selective pore typical of potassium channels. This channel has evolved to yield qualitatively different ion permeability ... The N.at-K v 3.2 potassium channel has an unusual weak inward rectifier phenotype. Several mutations of two amino acids in the ... The typical selectivity filter in potassium channels is formed by a tetrameric arrangement of the carbonyl groups of the ...
Shaker Superfamily of Potassium Channels. *kappa-conotoxin PVIIA. Grant support. *GM 58187/GM/NIGMS NIH HHS/United States ... Electrostatic recognition and induced fit in the kappa-PVIIA toxin binding to Shaker potassium channel.. Huang X1, Dong F, Zhou ... and electrostatic calculations were performed to study the binding process of kappa-PVIIA to the Shaker potassium channel and ... BD simulations, guided by electrostatic interactions, led to an initial alignment between the toxin and the channel protein. MD ...
Shaker Superfamily of Potassium Channels. 1. + +. 263. Potassium Channels, Voltage-Gated. 1. + +. ...
Clinical-pathologic correlations in voltage-gated Kv1 potassium channel complex-subtyped autoimmune painful polyneuropathy. ... P/Q- and N-type calcium-channel antibodies: Oncological, neurological, and serological accompaniments. Zalewski, N. L., Lennon ...
Shaker Superfamily of Potassium Channels Shaker Superfamily of Potassium Channels Flagellin フラゲリン ...
McCormackT, McCormackK (1994) Shaker K+ channel beta subunits belong to an NAD(P)H-dependent oxidoreductase superfamily. Cell ... 2000) A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons. Proc Natl Acad Sci U S ... Mammalian Kvβ voltage-gated K+ channel regulatory subunits [56], which belong to the aldo-keto reductase superfamily [57], [58] ... Variations of the SC-box are found in the human TASK-1 and TASK-3 channels and in two Drosophila two-pore domain K+ channels ( ...
NAB Domain Is Essential for the Subunit Assembly of both α-α and α-β Complexes of Shaker-like Potassium Channels ... The VGL-Chanome: A Protein Superfamily Specialized for Electrical Signaling and Ionic Homeostasis ... Kvβ1 Subunit Binding Specific for Shaker-Related Potassium Channel α Subunits ... Cortisone dissociates the Shaker family K+ channels from their β subunits. Yaping Pan, Jun Weng, Venkataraman Kabaleeswaran, ...
A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS. ... Potassium Channels: 2108*Voltage-Gated Potassium Channels: 446*Shaker Superfamily of Potassium Channels*Kv1.2 Potassium Channel ... Potassium Channels: 2108*Voltage-Gated Potassium Channels: 446*Shaker Superfamily of Potassium Channels*Kv1.2 Potassium Channel ... Potassium Channels: 2108*Voltage-Gated Potassium Channels: 446*Delayed Rectifier Potassium Channels: 12*Kv1.2 Potassium Channel ...
  • The movement of four S4s, one from each identical subunit of Shaker, is coupled to the "gate" which opens and closes the pore. (illinois.edu)
  • Primary structure of a beta subunit of alpha-dendrotoxin-sensitive K+ channels from bovine brain. (pnas.org)
  • Loss-of-function mutations in the Caenorhabditis elegans gene sup-18 suppress the defects in muscle contraction conferred by a gain-of-function mutation in SUP-10, a presumptive regulatory subunit of the SUP-9 two-pore domain K + channel associated with muscle membranes. (prolekare.cz)
  • Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. (ebi.ac.uk)
  • Additionally, the background K+ channel subunit TASK-1, which comprises four transmembrane segments and two pore domains, is also involved in both oxygen- and acid-sensing in peripheral chemoreceptors. (antibody-antibodies.com)
  • However, the proportions of the different syndromes, the numbers with associated tumours and the relationships with potassium channel subunit antibody specificities have been unclear. (ox.ac.uk)
  • 1989) of what is now known to be the CNG channel α subunit facilitated its molecular characterization. (ubc.ca)
  • Expression in mammalian cells helped resolve confusion regarding the JVL of the rod CNG channel a subunit. (ubc.ca)
  • PCR was used to construct cDNA clones which code for both the 63 and 80 kDa forms of the a subunit of the rod CNG channel. (ubc.ca)
  • The cloned CNG channel β subunit cDNA codes for a protein with a predicted molecular mass of 155 kDa (Korschen et al, 1995). (ubc.ca)
  • The expressed a subunit reconstituted alone did not generate functional cGMP-gated channels. (ubc.ca)
  • The system presented here will be useful to further define CNG α and β subunit interactions and to carry out structure-function studies on the channel using a biochemical efflux assay. (ubc.ca)
  • Accessory potassium channel protein which modulates the activity of the pore-forming alpha subunit. (uniprot.org)
  • Moreover, FS stress-induced tyrosine phosphorylation of both the NR2B subunit of the NMDA subtype of glutamate receptor and the K + -channel subunit Kvβ2 was regulated by SIRPα. (jneurosci.org)
  • BK Ca channels are formed by subunit homotetramers, each comprising a conserved transmembrane voltage-sensing domain (VSD), a pore domain, and a large intracellular ligand-binding domain (Fig. 1), recently visualized by cryoelectron microscopy (Wang and Sigworth, 2009). (sciencedocbox.com)
  • Different Shaker family α-subunit genes generate distinct voltage-dependent K + currents when expressed in heterologous expression systems. (jneurosci.org)
  • Truncation of TRPV1, expression of cytosolic termini of TRPV1 or TRPV4 and construction of chimeric TRPV channel subunits revealed that the specificity and the affinity of the subunit interaction is synergistically provided by interaction modules located in the transmembrane domains and in the cytosolic termini. (biologists.org)
  • The subunit composition may influence the biophysical and regulatory properties of the resulting channel complex. (biologists.org)
  • These structures depict the binding site of the antidiabetic drug glibenclamide, indicate how Kir6.2 (inward-rectifying potassium channel 6.2) N-terminus participates in the coupling between the peripheral SUR1 (sulfonylurea receptor 1) subunit and the central Kir6.2 channel, reveal the binding mode of activating nucleotides, and suggest the mechanism of how Mg-ADP binding on nucleotide binding domains (NBDs) drives a conformational change of the SUR1 subunit. (bvsalud.org)
  • In contrast to another 32 superfamilies adopting this motif, AKRs do not require metal ions for functionality, and bind NAD(P)H cofactor in an extended anti-conformation so that they can catalyse 4-pro-R hydride transfer and thus belong to the large group of A-face oxidoreductases. (biomedcentral.com)
  • While some channels permit the passage of ions based solely on charge, the archetypal channel pore is just one or two atoms wide at its narrowest point. (wikidoc.org)
  • In addition, ion channels figure in a wide variety of biological processes that involve rapid changes in cells, such as cardiac , skeletal , and smooth muscle contraction , epithelial transport of nutrients and ions, T-cell activation and pancreatic beta-cell insulin release. (wikidoc.org)
  • Ion channels may be classified by the nature of their gating, the species of ions passing through those gates, and the number of gates (pores). (wikidoc.org)
  • The phenomenon of inward rectification of K ir channels is the result of high-affinity block by endogenous polyamines , namely spermine , as well as magnesium ions, that plug the channel pore at positive potentials, resulting in a decrease in outward currents. (wikipedia.org)
  • KCa1.1 (also called Slo, Slo1, and BK or maxi K channel are ion channels characterized by their large conductance of potassium ions (K+) through cell membranes (260 pS). (epfl.ch)
  • These channels are categorised physiologically based on their gating mechanisms (voltage-gated or ligand-gated) and the types of ions that they transport (e.g. (biomedcentral.com)
  • It is difficult to evaluate the extent to which differential Shaker family gene expression contributes to endogenous K + current diversity, because the specific Shaker family gene or genes responsible for a given K + current are still unknown for nearly all adult neurons. (jneurosci.org)
  • We built an ion channel identification + classification pipeline (called MuSICC), employing an optimised support vector machine (SVM) model and using the Kyoto Encyclopaedia of Genes and Genomes (KEGG) classification system. (biomedcentral.com)
  • In this final complex, the toxin is bound to the extracellular entrance of the channel along the pore axis via a combination of hydrophobic, hydrogen bonding, and electrostatic interactions. (nih.gov)
  • Specific site-directed mutagenesis experiments are suggested to verify and confirm the structure of the toxin-channel complex. (nih.gov)
  • Hongotoxin (HgTX) is an ion channel toxin, which blocks Shaker-type (Kv1) K+ channels. (wikipedia.org)
  • Hongotoxin belongs to the short scorpion toxin superfamily. (wikipedia.org)
  • The second measures distances between S4 sites and a scorpion toxin bound to the symmetric axis of the channel just above the pore. (illinois.edu)
  • Electrostatic recognition and induced fit in the kappa-PVIIA toxin binding to Shaker potassium channel. (nih.gov)
  • BD simulations, guided by electrostatic interactions, led to an initial alignment between the toxin and the channel protein. (nih.gov)
  • The final complex structure was stabilized through electrostatic interactions with the positively charged side chain of Lys7 of kappa-PVIIA deeply inserted into the channel pore and other hydrogen bonds and by hydrophobic interactions involving Phe9 and Phe23 of the toxin. (nih.gov)
  • The validity of the predicted structure for the complex was assessed by calculating the effects of mutating charged and polar residues of both the toxin and the channel protein, with the calculated effects correlating reasonably well with experimental data. (nih.gov)
  • Biochemical characterization revealed that BcsTx3 is a 50 amino acid peptide crosslinked by four disulfide bridges, and sequence comparison allowed BcsTx3 to be classified as a novel type of sea anemone toxin acting on K V channels. (tcdb.org)
  • 2013). BcsTx3 is a founder of a novel sea anemone toxin family of potassium channel blocker. (tcdb.org)
  • The toxin reversibly blocks channel activity by interacting at the external pore of the channel protein with an apparent Kd of 2.1 nM. (smartox-biotech.com)
  • Our results argue that block of voltage-gated K+ channels results from the binding of one toxin molecule, so that Lys27 enters the pore and interacts with K+ (or Na+) in the ion conduction pathway. (smartox-biotech.com)
  • The Shaker residues making the strongest contribution to toxin binding are located close to the pore-lining sequence, and more distant residues on both sides of this region influence CTX binding weakly, probably by an electrostatic mechanism. (smartox-biotech.com)
  • Kv1.3 channel blockade with the Vm24 scorpion toxin attenuates the CD4+ effector memory T cell response to TCR stimulation Cell Communication and Signaling, 16, 45. (unam.mx)
  • Examples include the N-terminal T1 domain of Shaker channels ( 5 ) and C-terminal domains (CTDs) of the ether-a-go-go (EAG) ( 6 ) and the inwardly rectifying (K IR ) channels ( 7 ). (pnas.org)
  • Whole-cell current recordings of K ir 2 inwardly-rectifying potassium channels expressed in an HEK293 cell . (wikipedia.org)
  • 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). (wikipedia.org)
  • Other inwardly rectifying channels, termed "strong inward rectifiers," carry very little outward current at all, and are mainly active at voltages negative to the K + reversal potential, where they carry inward current (the much larger currents below the 0 nA line in figure 1). (wikipedia.org)
  • By sensing the intracellular ADP/ATP ratio of β-cells, pancreatic K channels control insulin release and regulate metabolism at the whole body level. (bvsalud.org)
  • Receptors and Channels , 5 (5), 291-304. (elsevier.com)
  • In eukaryotic cells, K + channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes [ PMID: 1373731 ]. (ebi.ac.uk)
  • Selamectin works by replacing glutamate which normally interacts with receptors that open chloride channels at muscle synapses found in parasites. (bionity.com)
  • They may have agonistic or antagonistic effects on the receptors, block ion channel pores or disrupt the interaction with neighboring molecules. (scielo.br)
  • It can respond to transient Ca2+ increases ("sparks") originated by opening of Ca2+ channels or sarcoplasmic reticulum ryanodine receptors, and it has been observed to form clusters optimally positioned for such local responses, for which it seems to have been particularly designed by evolution since it responds to [Ca2+] in the µM range. (epfl.ch)
  • Neuronal electrical signals are generated by ion channels and shaped by the structure of the neuron itself. (psu.edu)
  • Analysis of ion channel and cAMP pathway mutants indicates that this temperature-dependent plasticity is mediated via neuronal activity changes linked to mechanisms controlled by the rutabaga -encoded adenylyl cyclase. (jneurosci.org)
  • Analysis of ion channel and cAMP pathway mutants reveals that this temperature-dependent plasticity is mediated by neuronal activity changes. (jneurosci.org)
  • These channels play an important role in both linking muscle excitation with contraction as well as neuronal excitation with transmitter release. (wikidoc.org)
  • Moreover, each type of neuronal BK channels are differentially sensitive to PKA-dependent phosphorylation. (epfl.ch)
  • Leptin activates BK channels via PI 3-kinase controlling neuronal excitability. (epfl.ch)
  • Here we report that the homologous voltage-gated potassium (Kv) channels also exhibit high temperature sensitivity comparable to that of TRPV1, which is detectable under specific conditions when the voltage sensor is functionally decoupled from the activation gate through either intrinsic mechanisms or mutations. (elifesciences.org)
  • Interestingly, mutations could tune Shaker channel to be either heat-activated or heat-deactivated. (elifesciences.org)
  • Mutations of the central Phe residue favored the closed KAT1 channel, whereas mutations affecting the countercharge centers favored the open channel. (plantphysiol.org)
  • Finally, we elucidated the mechanism behind two disease-associated mutations found in the cytosolic C-linker/binding domain portion of the HCN2 and HCN4 channels to gain a better understanding of how they influence cAMP binding and channel opening, and cause epilepsy and profound bradycardia, respectively. (ubc.ca)
  • This is the first example of reconstitution of a heterologously expressed cation channel into lipid vesicles for Ca²⁺ efflux measurements. (ubc.ca)
  • I move on to do postdoctoral work on the diversity and function of large-conductance calcium-activated (BK) channels in Dr. Richard Aldrich's lab at Stanford. (psu.edu)
  • Charybdotoxin (ChTx) is a 37 amino acid peptide isolated from the venom of the scorpion Leiurus quinquestriatus hebraeus that blocks voltage-gated and large conductance Ca 2+ activated K + channels K Ca 1.1 in nanomolar concentrations (IC 50 ~ 3 nM). (smartox-biotech.com)
  • This combination of computational methods permits the identification of two possible structural models of AgTx2 in complex with the Shaker K+ channel, additional structural analysis providing further evidence in favor of a single model. (nih.gov)
  • In this study, we exploit recent advances in structural genomics to calculate the sequence-based probability of the presence of putative domains in a number of ion channels. (rupress.org)
  • Analyses of the CTDs of 32 putative prokaryotic Na V sequences suggest that a CTD helical bundle is a structural feature conserved throughout the bacterial sodium channel family. (pnas.org)
  • We are also interested how the structural polarity of neurons evolved as it relates to directional signaling and ion channel distribution. (psu.edu)
  • The architectures of the ion channel families consist of four variations built upon a common pore-forming structural theme. (aspetjournals.org)
  • The vanilloid receptor-related TRP channels (TRPV1-6) mediate thermosensation, pain perception and epithelial Ca 2+ entry. (biologists.org)
  • Sequence analyses predict its CTD will consist of an unordered region followed by an α-helix, which has a propensity to form a multimeric coiled-coil motif, and which could form an association domain in the homotetrameric NaChBac channel. (pnas.org)