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.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.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.Potassium Channels, Inwardly Rectifying: Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.Chloride Channels: Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.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.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.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.Ligand-Gated Ion Channels: A subclass of ion channels that open or close in response to the binding of specific LIGANDS.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.Potassium Channels, Calcium-Activated: Potassium channels whose activation is dependent on intracellular calcium concentrations.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.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.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.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.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.Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.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).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.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.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.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.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.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.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.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.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).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.Kv1.2 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.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.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.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.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.Kv1.3 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.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.Kv1.1 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.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.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.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.Kinetics: The rate dynamics in chemical or physical systems.KCNQ1 Potassium Channel: A voltage-gated potassium channel that is expressed primarily in the HEART.KCNQ Potassium Channels: A family of delayed rectifier voltage-gated potassium channels that share homology with their founding member, KCNQ1 PROTEIN. KCNQ potassium channels have been implicated in a variety of diseases including LONG QT SYNDROME; DEAFNESS; and EPILEPSY.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.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.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.Sodium Channels: Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.Kv1.4 Potassium Channel: A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.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.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.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.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.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.Cations: Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.Shaw Potassium Channels: A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.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.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Degenerin Sodium Channels: A family of mechanosensitive sodium channels found primarily in NEMATODES where they play a role in CELLULAR MECHANOTRANSDUCTION. Degenerin sodium channels are structurally-related to EPITHELIAL SODIUM CHANNELS and are named after the fact that loss of their activity results in cellular degeneration.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.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.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.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.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.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Acid Sensing Ion Channel Blockers: A subclass of sodium channel blockers that are specific for ACID-SENSING SODIUM CHANNELS.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.Gramicidin: A group of peptide antibiotics from BACILLUS brevis. Gramicidin C or S is a cyclic, ten-amino acid polypeptide and gramicidins A, B, D are linear. Gramicidin is one of the two principal components of TYROTHRICIN.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.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.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)Chlorides: Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.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.Tetraethylammonium: A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)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.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.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.Biophysics: The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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).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.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Nerve Tissue ProteinsKCNQ3 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.Voltage-Gated Sodium Channels: A family of membrane proteins that selectively conduct SODIUM ions due to changes in the TRANSMEMBRANE POTENTIAL DIFFERENCE. They typically have a multimeric structure with a core alpha subunit that defines the sodium channel subtype and several beta subunits that modulate sodium channel activity.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.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.Calcium Channels, P-Type: CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.Biophysical Phenomena: The physical characteristics and processes of biological systems.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.Receptors, Nicotinic: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.Amiloride: A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)Charybdotoxin: A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Alamethicin: A cyclic nonadecapeptide antibiotic that can act as an ionophore and is produced by strains of Trichoderma viride. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Calcium Channels, R-Type: CALCIUM CHANNELS located in the neurons of the brain. They are inhibited by the marine snail toxin, omega conotoxin MVIIC.Sodium Channel Agonists: A class of drugs that stimulate sodium influx through cell membrane channels.Calcium Channels, Q-Type: CALCIUM CHANNELS located in the neurons of the brain.Voltage-Dependent Anion Channels: A family of voltage-gated eukaryotic porins that form aqueous channels. They play an essential role in mitochondrial CELL MEMBRANE PERMEABILITY, are often regulated by BCL-2 PROTO-ONCOGENE PROTEINS, and have been implicated in APOPTOSIS.Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis.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.Mechanotransduction, Cellular: The process by which cells convert mechanical stimuli into a chemical response. It can occur in both cells specialized for sensing mechanical cues such as MECHANORECEPTORS, and in parenchymal cells whose primary function is not mechanosensory.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.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.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.Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion.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.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.Sulfonylurea Receptors: ATP-BINDING CASSETTE PROTEINS that are highly conserved and widely expressed in nature. They form an integral part of the ATP-sensitive potassium channel complex which has two intracellular nucleotide folds that bind to sulfonylureas and their analogs.Receptors, Purinergic P2X2: A purinergic P2X neurotransmitter receptor involved in sensory signaling of TASTE PERCEPTION, chemoreception, visceral distension and NEUROPATHIC PAIN. The receptor comprises three P2X2 subunits. The P2X2 subunits also have been found associated with P2X3 RECEPTOR subunits in a heterotrimeric receptor variant.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.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.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.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.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.Channelopathies: A variety of neuromuscular conditions resulting from MUTATIONS in ION CHANNELS manifesting as episodes of EPILEPSY; HEADACHE DISORDERS; and DYSKINESIAS.Heavy Ions: Positively-charged atomic nuclei that have been stripped of their electrons. These particles have one or more units of electric charge and a mass exceeding that of the Helium-4 nucleus (alpha particle).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.NAV1.4 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of SKELETAL MYOCYTES. Defects in the SCN4A gene, which codes for the alpha subunit of this sodium channel, are associated with several MYOTONIC DISORDERS.Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake.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.Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.Receptors, Serotonin, 5-HT3: A subclass of serotonin receptors that form cation channels and mediate signal transduction by depolarizing the cell membrane. The cation channels are formed from 5 receptor subunits. When stimulated the receptors allow the selective passage of SODIUM; POTASSIUM; and CALCIUM.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Dihydropyridines: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.Ion Pumps: A general class of integral membrane proteins that transport ions across a membrane against an electrochemical gradient.Electric Stimulation: Use of electric potential or currents to elicit biological responses.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.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.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.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.Receptors, Glycine: Cell surface receptors that bind GLYCINE with high affinity and trigger intracellular changes which influence the behavior of cells. Glycine receptors in the CENTRAL NERVOUS SYSTEM have an intrinsic chloride channel and are usually inhibitory.Ganglia, Spinal: Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain.Myocytes, Cardiac: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).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.NAV1.8 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that is expressed in nociceptors, including spinal and trigeminal sensory neurons. It plays a role in the transmission of pain signals induced by cold, heat, and mechanical stimuli.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.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.Receptors, Purinergic P2X: A subclass of purinergic P2 receptors that signal by means of a ligand-gated ion channel. They are comprised of three P2X subunits which can be identical (homotrimeric form) or dissimilar (heterotrimeric form).Permeability: Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.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)Tetraethylammonium Compoundsomega-Conotoxin GVIA: A neurotoxic peptide, which is a cleavage product (VIa) of the omega-Conotoxin precursor protein contained in venom from the marine snail, CONUS geographus. It is an antagonist of CALCIUM CHANNELS, N-TYPE.Heart: The hollow, muscular organ that maintains the circulation of the blood.Large-Conductance Calcium-Activated Potassium Channel beta Subunits: The regulatory subunits of large-conductance calcium-activated potassium channels.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)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.Saxitoxin: A compound that contains a reduced purine ring system but is not biosynthetically related to the purine alkaloids. It is a poison found in certain edible mollusks at certain times; elaborated by GONYAULAX and consumed by mollusks, fishes, etc. without ill effects. It is neurotoxic and causes RESPIRATORY PARALYSIS and other effects in MAMMALS, known as paralytic SHELLFISH poisoning.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.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.Torpedo: A genus of the Torpedinidae family consisting of several species. Members of this family have powerful electric organs and are commonly called electric rays.Water: A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)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.Cystic Fibrosis Transmembrane Conductance Regulator: A chloride channel that regulates secretion in many exocrine tissues. Abnormalities in the CFTR gene have been shown to cause cystic fibrosis. (Hum Genet 1994;93(4):364-8)Receptors, Purinergic P2: A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.Mesylates: Organic salts or esters of methanesulfonic acid.Phosphatidylinositol 4,5-Diphosphate: A phosphoinositide present in all eukaryotic cells, particularly in the plasma membrane. It is the major substrate for receptor-stimulated phosphoinositidase C, with the consequent formation of inositol 1,4,5-triphosphate and diacylglycerol, and probably also for receptor-stimulated inositol phospholipid 3-kinase. (Kendrew, The Encyclopedia of Molecular Biology, 1994)Porosity: Condition of having pores or open spaces. This often refers to bones, bone implants, or bone cements, but can refer to the porous state of any solid substance.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Sensory Receptor Cells: Specialized afferent neurons capable of transducing sensory stimuli into NERVE IMPULSES to be transmitted to the CENTRAL NERVOUS SYSTEM. Sometimes sensory receptors for external stimuli are called exteroceptors; for internal stimuli are called interoceptors and proprioceptors.Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Static Electricity: The accumulation of an electric charge on a objectMechanoreceptors: Cells specialized to transduce mechanical stimuli and relay that information centrally in the nervous system. Mechanoreceptor cells include the INNER EAR hair cells, which mediate hearing and balance, and the various somatosensory receptors, often with non-neural accessory structures.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)Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Neurons, Afferent: Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM.Sarcolemma: The excitable plasma membrane of a muscle cell. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Spider Venoms: Venoms of arthropods of the order Araneida of the ARACHNIDA. The venoms usually contain several protein fractions, including ENZYMES, hemolytic, neurolytic, and other TOXINS, BIOLOGICAL.Batrachotoxins: Batrachotoxin is the 20-alpha-bromobenzoate of batrachotoxin A; they are toxins from the venom of a small Colombian frog, Phyllobates aurotaenia, cause release of acetylcholine, destruction of synaptic vesicles and depolarization of nerve and muscle fibers.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.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.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.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)Mibefradil: A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE.Cation Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of positively charged molecules (cations) across a biological membrane.Receptors, Cholinergic: Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology.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.omega-Conotoxins: A family of structurally related neurotoxic peptides from mollusk venom that inhibit voltage-activated entry of calcium into the presynaptic membrane. They selectively inhibit N-, P-, and Q-type calcium channels.Receptors, Purinergic P2X4: A widely distributed purinergic P2X receptor subtype that plays a role in pain sensation. P2X4 receptors found on MICROGLIA cells may also play a role in the mediation of allodynia-related NEUROPATHIC PAIN.Electrochemistry: The study of chemical changes resulting from electrical action and electrical activity resulting from chemical changes.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Nitrobenzoates: Benzoic acid or benzoic acid esters substituted with one or more nitro groups.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.Connexins: A group of homologous proteins which form the intermembrane channels of GAP JUNCTIONS. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions.NAV1.1 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that is predominantly expressed in the CENTRAL NERVOUS SYSTEM. Defects in the SCN1A gene which codes for the alpha subunit of this sodium channel are associated with DRAVET SYNDROME, generalized epilepsy with febrile seizures plus, type 2 (GEFS+2), and familial hemiplegic migraine type 3.Aquaporins: A class of porins that allow the passage of WATER and other small molecules across CELL MEMBRANES.

Tetraethylammonium block of the BNC1 channel. (1/363)

The brain Na+ channel-1 (BNC1, also known as MDEG1 or ASIC2) is a member of the DEG/ENaC cation channel family. Mutation of a specific residue (Gly430) that lies N-terminal to the second membrane-spanning domain activates BNC1 and converts it from a Na+-selective channel to one permeable to both Na+ and K+. Because all K+ channels are blocked by tetraethylammonium (TEA), we asked if TEA would inhibit BNC1 with a mutation at residue 430. External TEA blocked BNC1 when residue 430 was a Val or a Thr. Block was steeply voltage-dependent and was reduced when current was outward, suggesting multi-ion block within the channel pore. Block was dependent on the size of the quaternary ammonium; the smaller tetramethylammonium blocked with similar properties, whereas the larger tetrapropylammonium had little effect. When residue 430 was Phe, the effects of tetramethylammonium and tetrapropylammonium were not altered. In contrast, block by TEA was much less voltage-dependent, suggesting that the Phe mutation introduced a new TEA binding site located approximately 30% of the way across the electric field. These results provide insight into the structure and function of BNC1 and suggest that TEA may be a useful tool to probe function of this channel family.  (+info)

Paradoxical stimulation of a DEG/ENaC channel by amiloride. (2/363)

Extracellular amiloride inhibits all known DEG/ENaC ion channels, including BNC1, a proton-activated human neuronal cation channel. Earlier studies showed that protons cause a conformational change that activates BNC1 and exposes residue 430 to the extracellular solution. Here we demonstrate that, in addition to blocking BNC1, amiloride also exposes residue 430. This result suggested that, like protons, amiloride might be capable of activating the channel. To test this hypothesis, we introduced a mutation in the BNC1 pore that reduces amiloride block, and found that amiloride stimulated these channels. Amiloride inhibition was voltage-dependent, suggesting block within the pore, whereas stimulation was not, suggesting binding to an extracellular site. These data show that amiloride can have two distinct effects on BNC1, and they suggest two different interaction sites. The results suggest that extracellular amiloride binding may have a stimulatory effect similar to that of protons in BNC1 or extracellular ligands in other DEG/ENaC channels.  (+info)

Cloning and functional expression of a novel degenerin-like Na+ channel gene in mammals. (3/363)

1. A degenerate polymerase chain reaction (PCR) homology screening procedure was applied to rat brain cDNA in order to identify novel genes belonging to the amiloride-sensitive Na+ channel and degenerin (NaC/DEG) family of ion channels. A single gene was identified that encodes a protein related to but clearly different from the already cloned members of the family (18-30 % amino acid sequence identity). Phylogenetic analysis linked this protein to the group of ligand-gated channels that includes the mammalian acid-sensing ion channels and the Phe-Met-Arg-Phe-amide (FMRFamide)-activated Na+ channel. 2. Expression of gain-of-function mutants after cRNA injection into Xenopus laevis oocytes or transient transfection of COS cells induced large constitutive currents. The activated channel was amiloride sensitive (IC50, 1.31 microM) and displayed a low conductance (9-10 pS) and a high selectivity for Na+ over K+ (ratio of the respective permeabilities, PNa+/PK+ >= 10), all of which are characteristic of NaC/DEG channel behaviour. 3. Northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed a predominant expression of its mRNA in the small intestine, the liver (including hepatocytes) and the brain. This channel has been called the brain-liver-intestine amiloride-sensitive Na+ channel (BLINaC). 4. Corresponding gain-of-function mutations in Caenorhabditis elegans degenerins are responsible for inherited neurodegeneration in the nematode. Besides the BLINaC physiological function that remains to be established, mutations in this novel mammalian degenerin-like channel might be of pathophysiological importance in inherited neurodegeneration and liver or intestinal pathologies.  (+info)

Molecular cloning, functional expression and chromosomal localization of an amiloride-sensitive Na(+) channel from human small intestine. (4/363)

Amiloride-sensitive Na(+) channels belonging to the recently discovered NaC/DEG family of genes have been found in several human tissues including epithelia and central and peripheral neurons. We describe here the molecular cloning of a cDNA encoding a novel human amiloride-sensitive Na(+) channel subunit that is principally expressed in the small intestine and has been called hINaC (human intestine Na(+) channel). This protein is similar to the recently identified rodent channel BLINaC and is relatively close to the acid sensing ion channels (ASICs) (79 and 29% amino acid identity, respectively). ASICs are activated by extracellular protons and probably participate in sensory neurons to nociception linked to tissue acidosis. hINaC is not activated by lowering the external pH but gain-of-function mutations can be introduced and reveal when expressed in Xenopus oocytes, an important Na(+) channel activity which is blocked by amiloride (IC(50)=0.5 microM). These results suggest the existence of a still unknown physiological activator for hINaC (e.g. an extracellular ligand). The presence of this new amiloride-sensitive Na(+) channel in human small intestine probably has interesting physiological as well as physiopathological implications that remain to be clarified. The large activation of this channel by point mutations may be associated with a degenerin-like behavior as previously observed for channels expressed in nematode mechanosensitive neurons. The hINaC gene has been mapped on the 4q31.3-q32 region of the human genome.  (+info)

Neuropeptide FF and FMRFamide potentiate acid-evoked currents from sensory neurons and proton-gated DEG/ENaC channels. (5/363)

Acidosis is associated with inflammation and ischemia and activates cation channels in sensory neurons. Inflammation also induces expression of FMRFamidelike neuropeptides, which modulate pain. We found that neuropeptide FF (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe amide) and FMRFamide (Phe-Met-Arg-Phe amide) generated no current on their own but potentiated H+-gated currents from cultured sensory neurons and heterologously expressed ASIC and DRASIC channels. The neuropeptides slowed inactivation and induced sustained currents during acidification. The effects were specific; different channels showed distinct responses to the various peptides. These results suggest that acid-sensing ion channels may integrate multiple extracellular signals to modify sensory perception.  (+info)

Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels. (6/363)

Acid sensing is associated with nociception, taste transduction, and perception of extracellular pH fluctuations in the brain. Acid sensing is carried out by the simplest class of ligand-gated channels, the family of H(+)-gated Na(+) channels. These channels have recently been cloned and belong to the acid-sensitive ion channel (ASIC) family. Toxins from animal venoms have been essential for studies of voltage-sensitive and ligand-gated ion channels. This paper describes a novel 40-amino acid toxin from tarantula venom, which potently blocks (IC(50) = 0.9 nm) a particular subclass of ASIC channels that are highly expressed in both central nervous system neurons and sensory neurons from dorsal root ganglia. This channel type has properties identical to those described for the homomultimeric assembly of ASIC1a. Homomultimeric assemblies of other members of the ASIC family and heteromultimeric assemblies of ASIC1a with other ASIC subunits are insensitive to the toxin. The new toxin is the first high affinity and highly selective pharmacological agent for this novel class of ionic channels. It will be important for future studies of their physiological and physio-pathological roles.  (+info)

Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+. (7/363)

Proton receptors of the acid-sensing ion channel (ASIC) family are expressed in sensory neurons and thus could play a critical role in the detection of noxious acidosis. To investigate the subunit composition of native ASICs in peripheral and central neurons, we co-injected human as well as rodent ASIC2a and ASIC3 subunits in Xenopus oocytes. The amplitudes of acid-induced biphasic responses mediated by co-expressed ASIC2a and ASIC3 subunits were much larger (as much as 20-fold) than the currents mediated by the respective homomers, clearly indicating functional association. The reversal potential of the ASIC2a+3 current (>/=+20 mV) reflected a cationic current mainly selective for sodium. The sensitivity to pH or amiloride of single versus co-expressed ASIC subunits was not significantly different; however, gadolinium ions inhibited ASIC3 and ASIC2a+3 responses with much higher potency (IC(50) approximately 40 microm) than the ASIC2a response (IC(50) >/=1 mm). Biochemical interaction between ASIC2a and ASIC3 subunits was demonstrated by co-purification from transfected human embryonic kidney (HEK293) cells and Xenopus oocytes. Our in situ hybridization data showed that rat ASIC2a and ASIC3 transcripts are co-localized centrally, whereas reverse transcription-polymerase chain reaction data led us to detect co-expression of human ASIC2a and ASIC3 subunits in trigeminal sensory ganglia, brain, and testis where they might co-assemble into a novel subtype of proton-gated channels sensitive to gadolinium.  (+info)

A novel strategy for cancer therapy by mutated mammalian degenerin gene transfer. (8/363)

Mammalian degenerin (MDEG) is a member of the amiloride-sensitive sodium ion channel family, and its site-directed active mutant (MDEG-G430F) induces massive Na+ influx into cells, leading to cell ballooning and cell bursting. We attempted a novel therapeutic approach for gastric cancers by transferring MDEG-G430F into cancer cells using tumor-specific promoters. In carcinoembryonic antigen (CEA)-producing gastric cancer cells, the level of cell death observed when MDEG-G430F was used with a CEA promoter was similar to that observed when using a potent nonspecific promoter such as the cytomegalovirus promoter. In an in vivo study, fusogenic liposome complexes containing MDEG-G430F driven by the CEA promoter were injected intraperitoneally into CEA-producing gastric cancer cells in a mouse peritoneal dissemination model. Although all 15 of the control mice were dead by 50 days postinoculation, 13 of the 15 mice treated with MDEG-G430F survived. These results indicate that transferring MDEG-G430F into cancer tissues using tumor-specific promoters can achieve striking and selective cancer cell death irrespective of the transcriptional efficiency of the promoters used in vivo, and suggest that this approach is a promising new strategy for cancer gene therapy.  (+info)

TY - JOUR. T1 - Neuroprotective Effects of Psalmotoxin-1, an Acid-Sensing Ion Channel (ASIC) Inhibitor, in Ischemia Reperfusion in Mouse Eyes. AU - Dibas, Adnan. AU - Millar, John Cameron. AU - Al-Farra, Abraham. AU - Yorio, Thomas. PY - 2018/7/3. Y1 - 2018/7/3. N2 - Purpose: The purpose of the current study is to assess changes in the expression of Acid-Sensing Ion Channel (ASIC)1a and ASIC2 in retinal ganglion cells (RGCs) after retinal ischemia and reperfusion (I/R) injury and to test if inhibition of ASIC1a provides RGC neuroprotection. Methods: Transient ischemia was induced in one eye of C57BL/6 mice by raising intraocular pressure to 120 mmHg for 60 min followed by retinal reperfusion by restoring normal pressure. RGC function was measured by Pattern electroretinography (PERG). In addition, retinal ASIC1a and ASIC2 were observed by immunohistochemistry and western blot. Changes in calpain, fodrin, heat shock protein 70 (HSP70), Brn3a, super oxide dismutase-1 (SOD1), catalase, and ...
Inside the organism, changes in pH levels occur under pathophysiological conditions such as inflammation, ischemia, cancer, and the like, which are accompanied by pain. The Acid-sensing Ion Channel (ASIC) detects changes in pH levels in the organism and transmits the pain signal to the brain. Biologically, many studies have been conducted regarding the Acid-sensing Ion Channel; however, many areas are still unclear, especially in terms of the operational mechanism and the cell membrane merging mechanism. Professor Suhs research team detected the cell membrane merging mechanisms that modulate the activity of the Acid-sensing Ion Channel at the molecular level, and it is this discovery and identification of the new cell membrane merging mechanism of the Acid-sensing Ion Channel that had remained unknown until now. The research team identified through animal experiments that there is a different cell membrane merging mechanism between subunits of the Acid-sensing Ion Channel. ASIC2a can be merged ...
Acid-sensing ion channels (ASICs) are trimeric, sodium-selective channels activated by extracellular protons. Although ASICs are intriguing molecular targets for pharmacological agents, there remains a lack of selective compounds that differentiate ASIC subtypes. The peripherally located ASIC3 activates with the simple removal of calcium. Additionally, nonproton ligands, like 2-guanidine-4-methylquinazoline (GMQ), have been identified to selectively activate ASIC3 via the nonproton ligand sensor domain (NPLSD). A pair of glutamates in rat ASIC3 (E79 and E423) responsible for GMQ activation is present in ASIC1, despite having no direct modulation effect on the channel. We proposed that nonproton ligand activation of ASIC1 may be state dependent, and relies on expansion of the NPLSD in order for GMQ to reach the binding site and exert its effects. We utilized two features of ASICs in order to test our hypothesis with whole cell and outside out patch-clamp electrophysiology. First, we induced a persistent
Pathophysiological conditions such as inflammation, ischemia, infection and tissue injury can all evoke pain, and each is accompanied by local acidosis. Acid sensing ion channels (ASICs) are proton-gated cation channels expressed in both central and peripheral nervous systems. Increasing evidence suggests that ASICs represent essential sensors for tissue acidosis-related pain. This review provides an update on the role of ASICs in pain sensation and discusses their therapeutic potential for pain management.
The IUPHAR/BPS Guide to Pharmacology. ASIC3 - Acid-sensing (proton-gated) ion channels (ASICs). Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
Vol 9: Restrictive Expression of Acid-Sensing Ion Channel 5 Asic5 in Unipolar Brush Cells of the Vestibulocerebellum.. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Curcumin, a major bioactive component of turmeric, has diverse therapeutic effects such as anti-inflammatory, antioxidant, anticancer, and antinociceptive activities. The acid-sensing ion channels...
Fang Qiu.,Chun-Yu Qiu.,Huilan Cai.,Ting-Ting Liu.,Zu-Wei Qu.,...&Wang-Ping Hu.(3111).Oxytocin inhibits the activity of acid-sensing ion channels through the vasopressin-1a receptor in primary sensory neurons1.出版物(0),1-34 ...
A growing number of ion channels, particularly those native to neuronal and glial cell types, are now known to respond to fluctuations in extracellular [Ca2+]. Among these are the ASIC1a/ASIC1b, proton-gated cation channels permeable to Na+ and Ca2+ found in central and peripheral nerves (Babini et al., 2002). Interestingly, these are modulated by modest changes not only in extracellular Ca2+ but also in extracellular Mg2+ and polycations such as spermine. Xiong et al. recently provided evidence that ASIC1a is the key link between ischemia, acidosis and the injurious effects of ischemia in the brain, owing to the influx of toxic levels of Ca2+ into the cells during activation of the proton-gated channel (Xiong et al., 2004). Note that ischemia might be a condition under which derangements in extracellular [Ca2+], as well as interstitial pH, also occur (Imadojemu et al., 2004).. Novel non-selective cation channels sensitive to external Ca2+ have also been identified in hippocampal neurons (Xiong ...
Unlike AB5, AB4.1, although being proton-sensitive, produced dramatically smaller pH 4 gated currents compared with ASIC2a and demonstrated a large shift in its proton sensitivity. AB4.1 contains an additional 21 amino acids of ASIC2b compared with AB5, and lacks the following potentially protonatable sites that are expressed by the equivalent ASIC2a sequence: H145, E155, and H158. In the domain exchanged in AB4.1, there is little sequence conservation between ASIC subunits, with the exception of residues shared between ASIC2a and ASIC1a. Residues H145 and E155 are conserved between ASIC2a and ASIC1a, but not with other ASIC subunits. Residue 158 is highly variable among the mammalian ASICs, and thus, lack of this histidine is unlikely to account for ASIC2b insensitivity, and we have previously shown that mutation H158 in ASIC2a (as well as H145 and E155) did not have any significant impact upon ASIC2a proton sensitivity (Smith et al., 2007). Within the 21 ASIC2b amino acids that differentiate ...
ASICs are permeable to cations and are activated by extracellular acidosis. They are subject to modulation by extracellular alkalosis, intracellular pH and various other factors. Much of what we know about these channels properties comes from expressing recombinant ASIC subunits in heterologous cells. Channels are formed by combinations of ASIC subunits in homotrimeric or heterotrimeric complexes, with different subunits conferring distinct properties (TABLE 1). The amino acid sequences of ASIC subunits are well conserved between species, in fact the mouse ASIC 1a and the human ASIC 1a share over 99% of their amino acid sequence identity. The recently described crystal structure of the chicken ASIC1 homomultimeric channel has shed light on the subunit interactions and, along with sequence homology analyses, has driven numerous structure-function experiments that are revealing how the channels respond to pH and other stimuli. In addition to the non-covalent inter-subunit interactions, disulphide ...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
Acid-sensing ionic channels (ASICs) have been shown to have a significant role in a growing number of physiological and pathological processes, such as nociception, synaptic transmission and plasticity, mechano-sensation and acidosis-induced neuronal injury. The discovery of pharmacological agents targeting ASICs has significant therapeutic potential and use as a research tool. In our work, we studied the action of transient perfusion (5 to 15 s) of aminoglycosides (AGs) (streptomycin and neomycin) on the proton-gated ionic currents in dorsal root ganglion neurons (DRG) of the rat and in HEK-293 cells. In DRG neurons, streptomycin and neomycin (30 μM) produced a significant, concentration-dependent and reversible reduction in the amplitude of the proton-gated current, and a slowing of the desensitization rate of the ASIC current. Gentamycin (30 μM) also showed a significant reversible action on the ASIC currents. The curves of the pH-effect for streptomycin and neomycin indicated that their ...
This toxin is a gating modifier that acts principally as an inhibitor on ASIC1a (ASIC isoform 2) and a potentiator on ASIC1b (ASIC isoform 3) (PubMed:10829030, PubMed:15955877, PubMed:21036899). This toxin potently and selectively inhibits rat, mouse and human ASIC1a (IC(50)=0.35-3.7 nM) (PubMed:10829030, PubMed:15955877, PubMed:21715637, PubMed:26248594, PubMed:21825095). The blockade is rapidly reversible (PubMed:10829030, PubMed:28320941). The toxin acts by shifting its steady-state desensitization to more alkaline pH (0.27 pH unit) (PubMed:15955877, PubMed:16505147). At higher concentrations, it potentiates rat and human ASIC1b and activates chicken ASIC1 by stabilizing the open state of these subtypes (PubMed:16505147, PubMed:21036899, PubMed:19185346, PubMed:24262969, PubMed:22842900). The toxin binds most tightly to the open and the desensitized states of ASIC1a (promoting desensitization), whereas it binds most tightly to the open state of ASIC1b (promoting opening) (PubMed:16505147). The toxin
Previous studies have identified a number of mutants and/or motifs that affect ASIC channel trafficking and/or function [28-34]. Most of these studies focused on ASIC1a. Our results demonstrated that the LL motifs in ASIC2a are important for its trafficking and function. All the mutants that we studied here had increased surface level (Fig. 1). However, only the DAA mutant exhibited a significant increase in surface:total ratio while the AADAA mutant had a marginal effect (p = 0.049). These data, together with our current recordings, indicate that most of the effect on ASIC2a surface trafficking and channel function was mainly mediated by the second LL motif. We speculate that the exact location of the LL motif may contribute to the differences observed between mutating the two LL motifs. It remains unclear as to the exact mechanism of how the LL motifs regulate ASIC2a. Our data here showed that the AADAA and DAA mutants increased the maturation of N-linked glycans. N-glycosylation is an ...
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Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may regulate delivery and recycling of proteins to the correct membrane domains. The tripartite complex composed of LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 may have the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Ensures the proper localization of GRIN2B (subunit 2B of the NMDA receptor) to neuronal postsynaptic density and may function in localizing synaptic vesicles at synapses where it is recruited by beta-catenin and cadherin. Required to localize Kir2 channels, GABA transporter (SLC6A12) and EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 to the basolateral membrane of epithelial cells. May increase the amplitude of ASIC3 acid-evoked currents by stabilizing the channel at the cell surface (By similarity ...
Overall this suggests that drugs targeted at one particular kind of channel (Acid-sensing ion channel 1), such as amiloride, could help reduce the level of nerve damage caused by multiple sclerosis. "We are in the process of setting up the clinical trial and hope to start next year," said Prof Fugger. "It is too early to say how many patients will be enrolled ...
ASICs (Acid Sensing Ion Channels) are of particular interest because they are directly activated by extracellular acidity, which is a major cause of pain. Indeed, many painful conditions such as ischemia, inflammation, tumor development or tissue incision are accompanied by tissue acidification. ASIC are excitatory ion channels that are expressed in neurons, including nociceptive sensory neurons. In humans, the use of amiloride, a nonspecific inhibitor of ASICs, has demonstrated their role in the perception of pain induced by subcutaneous injections of acidic solutions. ASICs thus appear as new candidates capable of mediating pain in humans. A growing number of data suggests that, in addition to protons, ASICs may also be activated by one or more endogenous compounds produced during inflammation. The purpose of this research project is to identify these compounds by testing the effects of human inflammatory exudates on ASICs activity. The discovery of such compounds would definitely validate ...
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Complete information for ASIC2 gene (Protein Coding), Acid Sensing Ion Channel Subunit 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway. The GATOR1 complex strongly increases GTP hydrolysis by RRAGA and RRAGB within RRAGC-containing heterodimers, thereby deactivating RRAGs, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling. The GATOR1 complex is negatively regulated by GATOR2 the other GATOR subcomplex in this amino acid-sensing branch of the TORC1 pathway ...
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use AnyEvent::RabbitMQ; my $cv = AnyEvent-,condvar; my $ar = AnyEvent::RabbitMQ-,new-,load_xml_spec()-,connect( host =, localhost, port =, 5672, user =, guest, pass =, guest, vhost =, /, timeout =, 1, on_success =, sub { $ar-,open_channel( on_success =, sub { my $channel = shift; $channel-,declare_exchange( exchange =, test_exchange, on_success =, sub { $cv-,send(Declared exchange); }, on_failure =, $cv, ); }, on_failure =, $cv, on_close =, sub { my $method_frame = shift-,method_frame; die $method_frame-,reply_code, $method_frame-,reply_text; } ); }, on_failure =, $cv, on_read_failure =, sub {die @_}, on_close =, sub { my $method_frame = shift-,method_frame; die $method_frame-,reply_code, $method_frame-,reply_text; }, ); print $cv-,recv, \n ...
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ASIC; ASIC1a; brain sodium channel 2 (BNC2, BNaC2); ASIC1b: ASICβ; ASIC2a: mammalian degenerin 1 (MDEG1), brain sodium channel 1 (BNC1, BNaC1); ASIC2b: mammalian degenerin 2 (MDEG2); ASIC3:...
Amiloride-sensitive cation channel 1, neuronal (degenerin), also known as ACCN1, is a human gene.[1] This gene encodes a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. The members of this family are amiloride-sensitive sodium channels that contain intracellular N and C termini, 2 hydrophobic transmembrane regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. The member encoded by this gene may play a role in neurotransmission. In addition, a heteromeric association between this member and ACCN3 (variant 1) has been observed to co-assemble into proton-gated channels sensitive to gadolinium. Alternative splicing has been observed at this locus and two variants, encoding distinct isoforms, have been identified.[1] ...
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The Epithelial Na+ Channel (ENaC) Family (TC 1.A.06) The ENaC family consists of sodium channels from animals and has no recognizable homologues in other eukaryotes or bacteria. The vertebrate ENaC proteins from epithelial cells cluster tightly together on the phylogenetic tree: voltage-insensitive ENaC homologues are also found in the brain. Eleven sequenced C. elegans proteins, including the degenerins, are distantly related to the vertebrate proteins as well as to each other. At least some of these proteins form part of a mechano-transducing complex for touch sensitivity. Other members of the ENaC family, the acid-sensing ion channels, ASIC1-3, are homo- or hetero-oligomeric neuronal H+-gated channels that mediate pain sensation in response to tissue acidosis. The homologous Helix aspersa (FMRF-amide)-activated Na+ channel is the first peptide neurotransmitter-gated ionotropic receptor to be sequenced. Mammalian ENaC is important for the maintenance of Na+ balance and the regulation of blood ...
Recent studies have shown that the acid-sensing ion channel 1 (ASIC1) contributes to the axonal degeneration in CNS lesions Physiologically, ASIC1 has been described as a postsynaptic proton receptor on hippocampal neurons influencing the intracellular Ca2+ concentration. In MS, ASIC1 seems to activate under acidic conditions predominating in the inflammatory CNS lesions leading to a Na+ and Ca2+ overload and consecutive damage and apoptosis of axons. Consecutively, in a MS mousemodel axonal damage was significantly less pronounced after administering amiloride, a clinically safe blocker of ASICs. So ASIC1 seems to play a major role in axonal degeneration in MS. To our knowledge no clinical studies have tested those promising in vitro results in humans so far.. Only one retrospective registry-based cohort study was performed. This study showed no difference in the risk of incident MS or hospitalization and death among MS patients using amilorid compared to those using thiazide diuretics. ...
cytoplasmic vesicle, plasma membrane, ion channel inhibitor activity, cellular response to leukemia inhibitory factor, negative regulation of acid-sensing ion channel activity, SMAD protein signal transduction
Inhibition of acid-sensing ion channels by diminazene and APETx2 evoke partial and highly variable antihyperalgesia in a rat model of inflammatory pain ...
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Fig. 5. Proton-activated currents associated with AtMHX expression in vacuolar giant patches. (A) Patch from a vacuole of a transformed cell. Currents are activated by switching from a pH 7.7 solution to a pH 5.7 solution and back to pH 7.7. N-methyl-glucamine (NMG) is the only monovalent cation in solution. The pipette solution (pH 7.0; cytoplasmic membrane side) contains 2 mM Mg2 and 2 mM Ca2 ; the bath solution contains 0.5 mM Mg2 . (B) Typical current records for the same protocol in a vacuolar patch from a non-transformed cell. (C) Current-voltage relations for the proton-activated current in Figure 5A (2-1), whereby records were subtracted just before (1) and after (2) application of the pH 5.7 solution. In addition, the current- voltage relation is given for the reverse current observed on removing protons, whereby the subtracted records were obtained just after returning to pH 7.7 (3) and 30 s later when the current had decayed (4). (D) Current-voltage relation of the 10 times smaller current
HPLC Application #20745: Yarra 3µm SEC-3000 AcCN gradient wash before + after overlay of standard. Column used: Yarra™ 3 µm SEC-3000, LC Column 300 x 7.8 mm, Ea Part#: 00H-4513-K0
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Improving market financials and continuing end market demand are combining to push ASIC Design activity to new levels. The Basic SoC market is being driven by the emergence in the Internet of Things (IoT) and the need for silicon solutions for this segment. Mixed Signal ASIC designs have been growing for the last few years as more and more systems seek to interface to analog type real world functions.
Expression of ASIC5 (ACCN5, HINAC, INAC) in cancer tissue. The cancer tissue page shows antibody staining of the protein in 20 different cancers.
This is effectively the same definition as a gate array.. What makes a structured/platform ASIC different from a gate array is that in a gate array the predefined metal layers serve to make manufacturing turnaround faster. In a structured/platform ASIC the predefined metallization is primarily to reduce cost of the mask sets and is also used to make the design cycle time significantly shorter as well. For example, in a cell-based or gate-array design the user often must design power, clock, and test structures themselves; these are predefined in most Structured/Platform ASICs and therefore can save time and expense for the designer compared to gate-array. Likewise, the design tools used for structured/Platform ASIC can be substantially lower cost and easier (faster) to use than cell-based tools, because the tools do not have to perform all the functions that cell-based tools do. In some cases, the structured/platform ASIC vendor requires that customized tools for their device (for example, ...
Associazione Scientifica Italiana di Coniglicoltura ATTI - PROCEEDINGS GIORNATE DI CONIGLICOLTURA ASIC 2015 Forlì, aprile 2015 Salone internazionale avicolo e cunicolo - edizione 2015 In collaborazione
Non-elite runners would benefit more by not carrying fluids and focusing on having better form and efficiency in training runs of less than two hours. Another reason to not carry water on runs shorter than two hours is that research has indicated that more adaptation occurs when the organisms water content is 1-2% decreased. It is sometimes referred to as the "quart low" theory, although the unit "quart" should not be taken literally. So it is actually beneficial to lose some fluid during training so that you force the appropriate adaptation, become more efficient and increase your fitness. The "super-compensation effect" is not promoted when your body maintains the status quo of pre-training bout levels ...
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Date: Sat, 28 Dec 2019 16:13:18 -0800 From: Stephen Hemminger ,[email protected], To: Haiyang Zhang ,[email protected], Cc: [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected] Subject: Re: [PATCH net-next, 3/3] hv_netvsc: Name NICs based on vmbus offer sequence and use async probe On Sat, 28 Dec 2019 15:46:33 -0800 Haiyang Zhang ,[email protected], wrote: , - net = alloc_etherdev_mq(sizeof(struct net_device_context), , - VRSS_CHANNEL_MAX); , + snprintf(name, IFNAMSIZ, "eth%d", dev-,channel-,dev_num); , + net = alloc_netdev_mqs(sizeof(struct net_device_context), name, , + NET_NAME_ENUM, ether_setup, , + VRSS_CHANNEL_MAX, VRSS_CHANNEL_MAX); , + Naming is a hard problem, and best left to userspace. By choosing ethN as a naming policy, you potentially run into naming conflicts with other non netvsc devices like those passed through ...
The molecular mechanism of pH sensing by chemoreceptors is not clear, although it had been proposed to be mediated by a drop in intracellular pH of carotid body glomus cells, which inhibits a K+ current. Recently, pH-sensitive ion channels have been described in glomus cells that respond directly to extracellular acidosis. In this study, we investigated the possible molecular mechanisms of carotid body pH-sensing by recording the responses of glomus cells isolated from rat carotid body to rapid changes in extracellular pH using whole-cell patch-clamping technique. Extracellular acidosis evoked transient inward currents in glomus cells that were evident at pH 7.0 and half-activated (pH 50) at 6.3. The current had the characteristics of ASICs. It averaged 40.7±15.7 pA (n=5) at pH 5.0 and was blocked by the ASIC channel blocker amiloride (200 μm) to 2.5±1.6 pA. Na+ free bathing solution eliminated the current and a Ca2+ free buffer enhanced (P,0.05) the current at pH 6.0 from 18.5±2.2 to ...
Tissue acidosis is effective in causing chronic muscle pain. However, how muscle nociceptors contribute to the transition from acute to chronic pain is largely unknown. Here we showed that a single intramuscular acid injection induced a priming effect on muscle nociceptors of mice. The primed muscle nociceptors were plastic and permitted the development of long-lasting chronic hyperalgesia induced by a second acid insult. The plastic changes of muscle nociceptors were modality-specific and required the activation of acid-sensing ion channel 3 (ASIC3) or transient receptor potential cation channel V1 (TRPV1). Activation of ASIC3 was associated with increased activity of tetrodotoxin (TTX)-sensitive voltage-gated sodium channels but not protein kinase Cϵ (PKCϵ) in isolectin B4 (IB4)-negative muscle nociceptors. In contrast, increased activity of TTX-resistant voltage-gated sodium channels with ASIC3 or TRPV1 activation in NaV1.8-positive muscle nociceptors was required for the development of chronic
TY - JOUR. T1 - The effect of ASIC3 knockout on corticostriatal circuit and mouse self-grooming behavior. AU - Wu, Wei-Li. AU - Cheng, Sin Jhong. AU - Lin, Shing Hong. AU - Chuang, Yu Chia. AU - Huang, Eagle Yi Kung. AU - Chen, Chih Cheng. PY - 2019/1/29. Y1 - 2019/1/29. N2 - Stereotypic and/or repetitive behavior is one of the major symptoms of autism spectrum disorder (ASD). Increase of self-grooming behavior is a behavioral phenotype commonly observed in the mouse models for ASD. Previously, we have shown that knockout of acid-sensing ion channel 3 (ASIC3) led to the increased self-grooming behavior in resident-intruder test. Given the facts that ASIC3 is mainly expressed in the peripheral dorsal root ganglion (DRG) and conditional knockout of ASIC3 in the proprioceptors induced proprioception deficits. We speculate a hypothesis that stereotypic phenotype related to ASD, pararalled with striatal dysfunction, might be caused by proprioception defect in the peripheral sensory neuron origin. ...
The objective of this study was to evaluate creatine as an anti-nociceptive compound in an animal model of thermal and inflammatory pain. Creatine has the structural potential to interact with acid-sensing ion channel 3 (ASIC3), which have been involved in pain sensation modulation. Our hypothesis was that creatine will interact with ASIC3 leading to decreased nociception. Male and female C57BL/6J mice were supplemented with creatine (6.25g/kg diet) and tested for thermal hyperalgesia and inflammatory pain response. The latency to withdraw the tail during the thermal hyperalgesia test was unaffected by sex or diet. For the formalin test, males and females responded differently to the stimulus, and the female mice supplemented with creatine seemed to recover faster than the controls. These preliminary data suggest a potential effect of creatine and sex on inflammation-based nociception and can be used as a stepping stone for the development of ASIC-based therapeutics
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ASIC2 Antibody 17851-1-AP has been identified with ELISA, WB, IP. 17851-1-AP detected 70 kDa band in rat brain tissue with 1:200-1:1000 dilution...
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In this review we outline how automated patch clamping systems are continuing to evolve and are increasingly positioned at the centre of most ion channel discovery activities.
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p,,strong,BACKGROUND: ,/strong,Early life adversities are risk factors for anxiety disorders and for pain syndromes, which are, in turn, highly comorbid with anxiety disorders. Repeated cross-fostering mouse pups to adoptive lactating females induces epigenetic modification and heightened mRNA-expression of the acid-sensing-ion-channel-1 gene, altered nociception, and hypersensitivity to 6% carbon dioxide air mixtures, a trait marker of specific human anxiety disorders such as, most clearly and prominently, panic disorder.,/p,. ,p,,strong,AIMS: ,/strong,We hypothesized that the acid-sensing ion channel inhibitor amiloride can modulate repeated cross-fostering animals exaggerated responses to carbon dioxide and nociceptive thermal stimulation.,/p,. ,p,,strong,METHODS: ,/strong,Respiratory carbon dioxide sensitivity was assessed by plethysmography during 6% carbon dioxide air mixture challenges, and nociception was assessed by latency of paw withdrawal to thermal stimulation, in repeated ...
Rabbit monoclonal antibody raised against a human ACCN1 peptide using ARM Technology. A synthetic peptide of human ACCN1 is used for rabbit immunization.Customer or Abnova will decide on the preferred peptide sequence. (H00000040-K) - Products - Abnova
www.whitegatestud.co.uk Asics GEL-Quantum 180™ - Silver/Titanium/Mint Set your stride soaring in the ASICS® GEL-Quantum 180™ running shoe!Predecessor: None. Support Type: Neutral to underpronation (supination).Cushioning: Maximum cushioning.Surface: Road. Differential: 10 mm.Light, breathable textile and synthetic film upper materials. Nearly seamless upper design helps reduce the likelihood of irritation.Lace-up closure. Padded tongue and collar. Soft, breathable fabric lining
article{8816f1fb-c286-4fc9-98d2-89f14c3766ab, abstract = {,p,Hypoxia and acidosis are inherent stress factors of the tumor microenvironment and have been linked to increased tumor aggressiveness and treatment resistance. Molecules involved in the adaptive mechanisms that drive stress-induced disease progression constitute interesting candidates of therapeutic intervention. Here, we provide evidence of a novel role of heparan sulfate proteoglycans (HSPG) in the adaptive response of tumor cells to hypoxia and acidosis through increased internalization of lipoproteins, resulting in a lipid-storing phenotype and enhanced tumor-forming capacity. Patient glioblastoma tumors and cells under hypoxic and acidic stress acquired a lipid droplet (LD)-loaded phenotype, and showed an increased recruitment of all major lipoproteins, HDL, LDL, and VLDL. Stress-induced LD accumulation was associated with increased spheroid-forming capacity during reoxygenation in vitro and lung metastatic potential in vivo. On a ...
A transport convergence (TC) subsystem for use as a form of logical pipeline processor is disclosed. The TC subsystem includes a number of ASIC computing blocks interconnected through a local bus for transferring data objects used as a form of common data I/O for each ASIC. The data object includes both control and data portions. A TC scheduling circuit coordinates transfer of data objecst to and from a TC data object memory that is local or external. The TC data object memory is shared in common with all the ASIC blocks so that computation results from each ASIC TC signal processing circuit can be passed between other ASICs to form a logical pipeline. The data objects output from the TC subsystem are used by other processing subsystems in an xDSL communications system, including a software based ATM TC subsystem, and a physical medium dependent subsystem. In addition, the architecture of the TC subsystem is configured so that it can be shared by multiple ports in an xDSL system. The individual ASICs
Full text for this publication is not currently held within this repository. Alternative links are provided below where available. ...
What is difference between Ion Channel and Transporter? Ion channel involves in passive transportation of ions while, transporter involves active transportation
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Ligand-gated ion channels (LGICs) are a group of transmembrane ion channel proteins which open to allow ions such as Na+, K+, Ca2+, or Cl- t ...
The Beetle (ASIC) is a chip designed for the Large Hadron Collider, the giant particle accelerator designed to recreate the Big Bang. Its part of the quark-detection equipment in an experiment called "Large Hadron Collider beauty.". ...
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SAAB SPACE 3 M2 block diagram Address strap Control interface Configuration Reset Analog I/O interfaces Digital I/O user interface
Researchers have developed several sub-types of ion channels that allow inflammation and growth factors to trigger persistent pain.
Research on ion channels now crosses most traditional subject boundaries and involves a wide range of approaches including some of the latest techniques in biochemistry and molecular biology, as well as advanced electrophysiology and biophysics. This volume describes up-to-date practical information for some of the most essential and exciting approaches currently available.
Ion Channels in Health and Sickness. Edited by: Kaneez Fatima Shad. ISBN 978-1-78984-227-2, eISBN 978-1-78984-228-9, PDF ISBN 978-1-83881-642-1, Published 2018-10-10
Our Discovery Services portfolio offers the broadest selection of ion channel and epithelial current assays, with industry-leading expertise to match.
Give yourself an edge when you lace up the GEL-Venture® 6 running shoe! Predecessor: GEL-Venture 5. Support Type: Neutral to underpronation (supination). Cushioning: Lightweight, flexible response ...
Acid-sensing ion channel 3 (ASIC3) also known as amiloride-sensitive cation channel 3 (ACCN3) or testis sodium channel 1 (TNaC1 ... Hruska-Hageman AM, Benson CJ, Leonard AS, Price MP, Welsh MJ (2004). "PSD-95 and Lin-7b interact with acid-sensing ion channel- ... The ASIC3 gene is one of the five paralogous genes that encode proteins that form trimeric acid-sensing ion channels (ASICs) in ... Price MP, Thompson RJ, Eshcol JO, Wemmie JA, Benson CJ (2004). "Stomatin modulates gating of acid-sensing ion channels". J. ...
Acid-sensing ion channel 1 (ASIC1) also known as amiloride-sensitive cation channel 2, neuronal (ACCN2) or brain sodium channel ... with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel)". Biochem. J. 361 (Pt ... with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel)". Biochem. J. 361 (Pt ... "Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors". J. Clin. Invest. 110 (8 ...
2005). "Stomatin modulates gating of acid-sensing ion channels". J. Biol. Chem. 279 (51): 53886-91. doi:10.1074/jbc.M407708200 ...
... can bind to a particular isoform of the Acid Sensing Ion Channel, the Acid Sensing Ion Channel 1 (ASIC1). The ... "Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons". Proceedings of the National ... It can desensitize Acid Sensing Ion Channels (ASIC), which are proton-gated sodium channels. Psalmotoxin is a toxin produced in ... "Amiloride-insensitive currents of the acid-sensing ion channel-2a (ASIC2a)/ASIC2b heteromeric sour-taste receptor channel". The ...
Acid-sensing ion channels (ASICs) are also sensitive to inhibition by amiloride. ASICs are involved in nociceptor responses to ... A fraction of the effects of amiloride is inhibition of cyclic GMP-gated cation channels in the inner medullary collecting duct ... Amiloride works by directly blocking the epithelial sodium channel (ENaC) thereby inhibiting sodium reabsorption in the late ... of the action of angiotensin II on the secretion of hydrogen ions in proximal tubule cells. Amiloride was also tested as ...
... act as inhibitors for acid-sensing ion channels in the central and peripheral nervous system, causing a pain-inihibiting effect ... "Black mamba venom peptides target acid-sensing ion channels to abolish pain". Nature. 490 (7421): 552-555. doi:10.1038/ ... "Black Mamba: Kiss of Death". Smithsonian Channel. Retrieved 15 February 2015. The new encyclopedia of Reptiles (Serpent). Time ...
"Black mamba venom peptides target acid-sensing ion channels to abolish pain". Nature. 490 (7421): 552-555. doi:10.1038/ ... the mambalgin family of 3FTx proteins interacts with acid-sensing ion channels to produce analgesia without apparent toxic ... a family of ligand-gated ion channels. 3FTx binding interferes with cholinergic intercellular signaling particularly at ... The 3FP protein domain has no enzymatic activity and is typically between 60-74 amino acid residues long. Despite their ...
ASIC1a is an acid-sensing ion channel involved in the pain sensory pathway, which is regulated by p11. Although the exact ... "Annexin II light chain p11 promotes functional expression of acid-sensing ion channel ASIC1a". The Journal of Biological ... Ion channels are among the several proteins that are transported through the interaction with p11. Some of these proteins ... TASK-1 is a two-pore domain K+ channel TWIK-related acid-sensitive K (TASK). P11 can also function as a retention factor, ...
"X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na(+)-selective channel". Cell. 156 ( ... Jasti J, Furukawa H, Gonzales EB, Gouaux E (Sep 2007). "Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH ... Hanukoglu I (2017). "ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity ... Giraldez T, Rojas P, Jou J, Flores C, Alvarez de la Rosa D (Aug 2012). "The epithelial sodium channel δ-subunit: new notes for ...
Ion channels. Including: ATP-sensitive K+ channels, voltage-gated Ca2+ channels, and acid-sensing ion channels (ASICs). ... ion channels, nitric oxide (NO) synthesis and polyamine metabolism and this provides bases for further research into potential ... Due to its ability to pass through open cationic channels, agmatine has also been used as a surrogate metric of integrated ... When neural tissue is incubated in agmatine and an external stimulus is applied, only cells with open channels will be filled ...
Acid-sensing ion channel 2 (ASIC2) also known as amiloride-sensitive cation channel 1, neuronal (ACCN1) or brain sodium channel ... with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel)". The Biochemical ... The ASIC2 gene is one of the five paralogous genes that encode proteins that form trimeric acid-sensing ion channels (ASICs) in ... Price MP, Thompson RJ, Eshcol JO, Wemmie JA, Benson CJ (Dec 2004). "Stomatin modulates gating of acid-sensing ion channels". ...
"Acid-sensing ion channels (ASICs) 2 and 4.2 are expressed in the retina of the adult zebrafish". Cell and Tissue Research. 360 ... sources LED type Diopter configured to restrict electromagnetic radiations damaging the visual system Acid-sensing ion channels ...
"The multivalent PDZ domain-containing protein CIPP is a partner of acid-sensing ion channel 3 in sensory neurons". J. Biol. ...
Acid-sensing ion channel 4 (ASIC4) also known as amiloride-sensitive cation channel 4 (ACCN4) is a protein that in humans is ... "Zebrafish acid-sensing ion channel (ASIC) 4, characterization of homo- and heteromeric channels, and identification of regions ... The ASIC4 gene is one of the five paralogous genes that encode proteins that form trimeric acid-sensing ion channels (ASICs) in ... Gründer S, Geissler HS, Bässler EL, Ruppersberg JP (2000). "A new member of acid-sensing ion channels from pituitary gland". ...
Hruska-Hageman AM, Benson CJ, Leonard AS, Price MP, Welsh MJ (2004). "PSD-95 and Lin-7b interact with acid-sensing ion channel- ... "PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current". J. Biol. Chem. 279 ... Olsen O, Liu H, Wade JB, Merot J, Welling PA (2002). "Basolateral membrane expression of the Kir 2.3 channel is coordinated by ... Olsen O, Liu H, Wade JB, Merot J, Welling PA (Jan 2002). "Basolateral membrane expression of the Kir 2.3 channel is coordinated ...
2004). "PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current". J. Biol. ... "PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current". J. Biol. Chem. ... PDZ domains contain approximately 90 amino acids and bind the extreme C terminus of proteins in a sequence-specific manner.[ ... 2003). "The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane ...
"PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current". The Journal of ... "PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current". The Journal of ... Ridgway LD, Kim EY, Dryer SE (Jul 2009). "MAGI-1 interacts with Slo1 channel proteins and suppresses Slo1 expression on the ... Calcium-activated potassium channel subunit alpha-1, FCHSD2, LRP2, and SYNPO. ENSG00000151276 GRCh38: Ensembl release 89: ...
"X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na(+)-selective channel". Cell. 156 ( ... Jasti J, Furukawa H, Gonzales EB, Gouaux E (Sep 2007). "Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH ... Hanukoglu I (2017). "ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity ... "Human Nedd4 interacts with the human epithelial Na+ channel: WW3 but not WW1 binds to Na+-channel subunits". Biochem. J. 345 (3 ...
... gene is one of the five paralogous genes that encode proteins that form trimeric Acid-sensing ion channels (ASICs) in ... Hanukoglu I (2017). "ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity ... The pore of the channel through which ions selectively flow from the extracellular side into the cytoplasm is formed by the ... The protein encoded by this gene does not appear to be acid responsive. The cDNA coding for this protein was first ...
... with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel)". Biochem. J. 361 (Pt ... with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel)". Biochem. J. 361 (Pt ... "cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein ... Duggan A, Garcia-Anoveros J, Corey DP (2002). "The PDZ domain protein PICK1 and the sodium channel BNaC1 interact and localize ...
Two distinct types of mechanosensitive ion channels have been found in the posterior root ganglion neurons. The two channels ... Proton-sensing G protein-coupled receptors are expressed by DRG sensory neurons and might play a role in acid-induced ... Cho, H.; Shin, J.; Shin, C. Y.; Lee, S. Y.; Oh, U. (2002). "Mechanosensitive ion channels in cultured sensory neurons of ... In these sensory neurons, a group of ion channels thought to be responsible for somatosensory transduction have been identified ...
"X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na(+)-selective channel". Cell. 156 ( ... Jasti J, Furukawa H, Gonzales EB, Gouaux E (Sep 2007). "Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH ... The second N in the abbreviation (SCNN1) represents that these are NON-voltage-gated channels. In most vertebrates, sodium ions ... Hanukoglu I (2017). "ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity ...
Some ion channels will open to a low pH, and the acid sensing ion channel has been shown to open at body temperature, in a ... It is sometimes described as feeling like acid under the skin. Burning dysesthesia might accurately reflect an acidotic state ... abnormal sense of touch. It often presents as pain but may also present as an inappropriate, but not discomforting, sensation. ...
5-HT3 receptor ACCN1 ANO1 AP2 adaptor complex Aaron Klug Acid-sensing ion channel Activating function Active transport Adolf ... channel alpha 3 Cyclic nucleotide-gated channel alpha 4 Cyclic nucleotide-gated ion channel Cyclic nucleotide gated channel ... Voltage-gated ion channel Voltage-gated potassium channel Voltage-gated potassium channel database Voltage-gated proton channel ... Lecithin Lee Spetner Leslie Barnett Ligand-gated ion channel Light-gated ion channel Lignocellulosic biomass Limitations of ...
"X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na(+)-selective channel". Cell. 156 ( ... Jasti J, Furukawa H, Gonzales EB, Gouaux E (September 2007). "Structure of acid-sensing ion channel 1 at 1.9 A resolution and ... "A long isoform of the epithelial sodium channel alpha subunit forms a highly active channel". Channels. 9 (1): 30-43. doi: ... Hanukoglu I (February 2017). "ASIC and ENaC type sodium channels: conformational states and the structures of the ion ...
"There's real sense that this is not going to happen anytime soon," she says, "but it will happen, and it will create dramatic ... Propionic acid production by Propionibacterium acidipropionici immobilized on 3D-printed nylon beads was chosen as a model ... Research in lithium-ion batteries. *Silicon-air battery. *Thermal energy storage. *Ultracapacitor ... By the early 2010s, the terms 3D printing and additive manufacturing evolved senses in which they were alternate umbrella terms ...
The Acid-sensing Ion Channel (ASIC) detects changes in pH levels in the organism and transmits the pain signal to the brain. ... al., Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking of ASIC2b via Heteromeric Assembly, Scientific Reports ... Biologically, many studies have been conducted regarding the Acid-sensing Ion Channel; however, many areas are still unclear, ... That our study investigated a new control mechanism of the Acid-sensing Ion Channel has important implications. Through ...
Dibas, A, Millar, JC, Al-Farra, A & Yorio, T 2018, Neuroprotective Effects of Psalmotoxin-1, an Acid-Sensing Ion Channel (ASIC ... N2 - Purpose: The purpose of the current study is to assess changes in the expression of Acid-Sensing Ion Channel (ASIC)1a and ... AB - Purpose: The purpose of the current study is to assess changes in the expression of Acid-Sensing Ion Channel (ASIC)1a and ... Purpose: The purpose of the current study is to assess changes in the expression of Acid-Sensing Ion Channel (ASIC)1a and ASIC2 ...
  • Thus, GMQ activation was introduced in cASIC1 by replacing the transmembrane domains with those of ASIC3 suggesting that the ASIC3 TM domains dictate NPLSD influence on channel activity. (unt.edu)
  • Taken together, we identified that channel state influences nonproton ligand interaction with ASICs, and the transmembrane domains are critical for this interaction. (unt.edu)
  • A pair of glutamates in rat ASIC3 (E79 and E423) responsible for GMQ activation is present in ASIC1, despite having no direct modulation effect on the channel. (unt.edu)
  • Professor Byung-Chang Suh from DGIST's Department of Brain and Cognitive Sciences said, 'Understanding of the cell membrane merging and activity control mechanism of the Acid-sensing Ion Channel plays an important role in identifying the pain signal transmission system. (scienmag.com)
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