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.
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.
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.
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 where the flow of K+ ions into the cell is greater than the outward flow.
Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.
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.
A class of drugs that act by selective inhibition of calcium influx through cellular membranes.
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.
A subclass of ion channels that open or close in response to the binding of specific LIGANDS.
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 whose activation is dependent on intracellular calcium concentrations.
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.
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.
Voltage-gated potassium channels whose primary subunits contain six transmembrane segments and form tetramers to create a pore with a voltage sensor. They are related to their founding member, shaker protein, Drosophila.
A 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.
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.
The ability of a substrate to allow the passage of ELECTRONS.
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).
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.
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.
A major class of calcium activated potassium channels whose members are voltage-dependent. MaxiK channels are activated by either membrane depolarization or an increase in intracellular Ca(2+). They are key regulators of calcium and electrical signaling in a variety of tissues.
A 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.
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.
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.
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 that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.
Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).
A heterogenous group of transient or low voltage activated type CALCIUM CHANNELS. They are found in cardiac myocyte membranes, the sinoatrial node, Purkinje cells of the heart and the central nervous system.
A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.
Sodium channels found on salt-reabsorbing EPITHELIAL CELLS that line the distal NEPHRON; the distal COLON; SALIVARY DUCTS; SWEAT GLANDS; and the LUNG. They are AMILORIDE-sensitive and play a critical role in the control of sodium balance, BLOOD VOLUME, and BLOOD PRESSURE.
A 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.
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.
An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.
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.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
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.
The rate dynamics in chemical or physical systems.
A voltage-gated potassium channel that is expressed primarily in the HEART.
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.
A 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.
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.
A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.
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.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
A 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.
Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.
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.
Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.
A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.
Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.
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.
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.
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
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.
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.
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.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of CARDIOMYOCYTES. Defects in the SCN5A gene, which codes for the alpha subunit of this sodium channel, are associated with a variety of CARDIAC DISEASES that result from loss of sodium channel function.
A family of inwardly-rectifying potassium channels that are activated by PERTUSSIS TOXIN sensitive G-PROTEIN-COUPLED RECEPTORS. GIRK potassium channels are primarily activated by the complex of GTP-BINDING PROTEIN BETA SUBUNITS and GTP-BINDING PROTEIN GAMMA SUBUNITS.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A subclass of sodium channel blockers that are specific for ACID-SENSING SODIUM 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.
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.
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.
A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.
The 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)
Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.
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.
A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)
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.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A 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.
The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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).
The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
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.
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.
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.
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 located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.
The physical characteristics and processes of biological systems.
An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.
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.
A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.
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)
A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
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 located in the neurons of the brain. They are inhibited by the marine snail toxin, omega conotoxin MVIIC.
A class of drugs that stimulate sodium influx through cell membrane channels.
CALCIUM CHANNELS located in the neurons of the brain.
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.
Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis.
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.
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.
Elements of limited time intervals, contributing to particular results or situations.
An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.
The 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.
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.
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.
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.
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.
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.
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.
A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
The 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.
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.
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.
Proteins prepared by recombinant DNA technology.
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.
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.
A variety of neuromuscular conditions resulting from MUTATIONS in ION CHANNELS manifesting as episodes of EPILEPSY; HEADACHE DISORDERS; and DYSKINESIAS.
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).
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.
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.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.
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.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.
A general class of integral membrane proteins that transport ions across a membrane against an electrochemical gradient.
Use of electric potential or currents to elicit biological responses.
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.
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.
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.
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.
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.
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.
Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
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.
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.
Positively charged atoms, radicals or group of atoms with a valence of plus 1, which travel to the cathode or negative pole during electrolysis.
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).
Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.
Synthetic transcripts of a specific DNA molecule or fragment, made by an in vitro transcription system. This cRNA can be labeled with radioactive uracil and then used as a probe. (King & Stansfield, A Dictionary of Genetics, 4th ed)
A 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.
The hollow, muscular organ that maintains the circulation of the blood.
The regulatory subunits of large-conductance calcium-activated potassium channels.
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.
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)
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.
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.
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.
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.
A genus of the Torpedinidae family consisting of several species. Members of this family have powerful electric organs and are commonly called electric rays.
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)
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.
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)
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.
Organic salts or esters of methanesulfonic acid.
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)
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.
A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.
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.
Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.
The accumulation of an electric charge on a object
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.
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)
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
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)
A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.
The excitable plasma membrane of a muscle cell. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
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.
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.
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.
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 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.
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.
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)
A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE.
Membrane proteins whose primary function is to facilitate the transport of positively charged molecules (cations) across a biological membrane.
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.
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.
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.
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.
The study of chemical changes resulting from electrical action and electrical activity resulting from chemical changes.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Benzoic acid or benzoic acid esters substituted with one or more nitro groups.
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.
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.
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.
A class of porins that allow the passage of WATER and other small molecules across CELL MEMBRANES.
An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.

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.
TY - JOUR. T1 - Alterations in subcellular expression of acid-sensing ion channels in the rat forebrain following chronic amphetamine administration. AU - Suman, Ajay. AU - Mehta, Bhavi. AU - Guo, Ming Lei. AU - Chu, Xiang Ping. AU - Fibuch, Eugene E.. AU - Mao, Li Min. AU - Wang, John Q.. PY - 2010/9. Y1 - 2010/9. N2 - Acid-sensing ion channels (ASICs) are densely expressed in broad areas of mammalian brains and actively modulate synaptic transmission and a variety of neuronal activities. To explore whether ASICs are linked to addictive properties of drugs of abuse, we investigated the effect of the psychostimulant amphetamine on subcellular ASIC expression in the rat forebrain in vivo. Repeated administration of amphetamine (once daily for 7 days, 1.25. mg/kg for days 1/7, 4. mg/kg for days 2-6) induced typical behavioral sensitization. At a 14-day withdrawal period, ASIC1 protein levels were increased in the defined surface and intracellular compartments in the striatum (both caudate putamen ...
TY - JOUR. T1 - Acid-sensing ion channels contribute to the metaboreceptor component of the exercise pressor reflex. AU - McCord, Jennifer L.. AU - Tsuchimochi, Hirotsugu. AU - Kaufman, Marc P.. PY - 2009/7. Y1 - 2009/7. N2 - The exercise pressor reflex is evoked by both mechanical and metabolic stimuli arising in contracting skeletal muscle. Recently, the blockade of acid-sensing ion channels (ASICs) with amiloride and A-316567 attenuated the reflex. Moreover, amiloride had no effect on the mechanoreceptor component of the reflex, prompting us to determine whether ASICs contributed to the metaboreceptor component of the exercise pressor reflex. The metaboreceptor component can be assessed by measuring mean arterial pressure during postcontraction circulatory occlusion when only the metaboreceptors are stimulated. We examined the effects of amiloride (0.5 μg/kg), A-317567 (10 mM, 0.5 ml), and saline (0.5 ml) on the pressor response to and after static contraction while the circulation was ...
Acid-sensing ion channel 1b (ASIC1b) is a proton-gated Na(+) channel mostly expressed in peripheral sensory neurons. To date, the functional significance of ASIC1b in these cells is unclear due to the lack of a specific inhibitor/blocker. A better understanding of the regulation of ASIC1b may provid …
Subject: Role and regulation of ASIC channels in pain processes at the spinal cord level. Summary: ASICs (Acid-Sensing Ion Channels) are a family of excitatory ion channels (ASIC1 to ASIC3) widely expressed throughout the pain neuraxis. These channels are sensors of extracellular acidity and are activated by protons. Different subtypes of ASIC channels have been characterized in peripheral sensory neurons and nociceptors, the dorsal horn of the spinal cord or the brain. We have recently identified, in patients, endogenous lipids (Jacquot et al., 2021; Marra & Deval, 2016; Marra et al., 2016) capable of strongly modulating ASIC3 channel activity in the periphery, and of generating a chronic pain state in a preclinical model of joint pain (Jacquot et al., 2021). In this model, we were able to demonstrate a sensitization of spinal neurons and anxiety- pain comorbidity phenomena. This thesis project will study the role of central ASIC channels (mainly ASIC1 and ASIC2) in the mechanisms of central ...
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 ...
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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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that all of these other stimuli were exteroceptive in nature, mainly processed through visual and auditory pathways that project to the amygdala. In contrast, CO2 acts internally at acid-activated chemoreceptors and causes an array of physiological changes. Thus, CO2 might engage interoceptive afferent sensory pathways that project to the brainstem, diencephalon and insular cortex. In addition, many brain areas outside the amygdala possess CO2 and pH-sensitive chemoreceptors, including acid-sensing ion channels. Thus, CO2 may directly activate extra-amygdalar brain structures that underlie fear and panic, which may help to explain the apparent discrepancy between these findings and previous work in mice. In either case, our results indicate that, in humans, the internal threat signaled by CO2 is detected and interpreted as fear and panic despite the absence of an intact amygdala ...
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 ...
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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 ...
A clearing and settlement (CS) facility provides the mechanism for parties to a transaction in financial products to meet their obligations to each other. Anyone who operates a CS facility in Australia must obtain a licence to do so, or otherwise be exempted by the Minister (or an ASIC delegate).. ASIC is responsible for the supervision of operators CS facilities. We advise the Government (or an ASIC delegate) on changes to licensee operating rules and on applications for new CS facility licences.. ...
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An anti-zebrafish ASIC4b (zASIC4.2) polyclonal antibody against two peptides corresponding to regions near the NH2 terminus (aa 146-160; PKSRKGHRPSELQYP) and the COOH terminus (aa 519-533; CFEEVKVKAANDVAQP) of ASIC4.2 protein (accession no. Q708S3.1) was custom-made by 21st Century Biochemicals (Marlboro, MA). The polyserum was affinity-purified against each of these peptides independently. (Dymowska, A.K., Schultz, A.G., Blair, S.D., Chamot, D., Goss, G.G. ...
An anti-zebrafish ASIC4b (zASIC4.2) polyclonal antibody against two peptides corresponding to regions near the NH2 terminus (aa 146-160; PKSRKGHRPSELQYP) and the COOH terminus (aa 519-533; CFEEVKVKAANDVAQP) of ASIC4.2 protein (accession no. Q708S3.1) was custom-made by 21st Century Biochemicals (Marlboro, MA). The polyserum was affinity-purified against each of these peptides independently. (Dymowska, A.K., Schultz, A.G., Blair, S.D., Chamot, D., Goss, G.G. ...
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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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Amiloride-sensitive cation channel, ASIC1/ASIC3 (also called ASIC1a, BNC1, MDEG, ACCN2 and BNAC2), which is an acid-sensitive (proton-gated) homo- or hetero-oligomeric cation (Na+ (high affinity), Ca2+, K+) channel. It it 98% identical to the human ortholog and associates with DRASIC tomediate touch sensation, being a mechanosensor (lead inhibited) channel (Wang et al., 2006). In pulmonary tissue (lung epithelial cells) it and CFTR interregulate each other (Su et al., 2006). ASIC3 is a sensor of acidic and primary inflammatory pain (Deval et al., 2008). Acid sensing ion channel-1b (ASIC1b), virtually identical to the rat and human orthologs, is stimulated by hypotonic stimuli (Ugawa et al., 2007; Deval et al., 2008). This protein is 98% idientical to the human ortholog Z(as noted above), which is an excitatory neuronal cation channel, involved in physiopathological processes related to extracellular pH fluctuation such as nociception, ischaemia, perception of sour taste and synaptic ...
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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 ...
Exposure of animals to increased concentrations of CO2 induces fear responses, perhaps because it signals the possibility of suffocation. In humans, such exposure to CO2 can induce panic attacks in people with anxiety disorders. The brain region known as the amygdala processes neuronal signals associated with fear behaviors. Ziemann et al. now report that the amygdala itself may be the chemosensor that directly senses CO2 concentrations. Dissolved CO2 causes a decrease in the pH of the blood. Some of the authors had previously shown that the acid-sensing ion channel 1a (ASIC1a), a channel that is activated by extracellular acidosis, is expressed in abundance in the amygdala and other fear circuits in the brain. They therefore tested whether activation of ASIC1a channels in the amygdala might mediate fear responses to inhalation of CO2. Indeed, in four models of fear behavior in mice, knockout animals not expressing ASIC1a showed decreased fear responses to increased concentrations of CO2. ...
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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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, ...
A budget-friendly reagent pack containing antibodies, ASIC3 channel-expressing membrane lysates & biologically active channel activator & blockers.
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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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  • Acid-sensing ion channels (ASICs) are permeable to Na + (and other cations), activated by low extracellular pH and widely expressed in the CNS and the peripheral nervous system (PNS). (
  • In large part, this question has driven increasing investigation on acid-sensing ion channels (ASICs) in the CNS and the peripheral nervous system for the past two decades. (
  • Acid-sensing ion channels (ASICs) are proton-gated cation channels that are predominantly expressed in the nervous system. (
  • ASICs are involved in a number of neurological diseases such as pain, ischemic stroke and multiple sclerosis but limited tools are available to target these channels and provide probes for their physiological functions. (
  • Acid-sensing ion channels (ASICs) are neuronal voltage-insensitive sodium channels activated by extracellular protons permeable to Na+. (
  • Acid-sensing ion channels (ASICs) are proton-gated ion channels that are highly expressed in the nervous system and play important roles in physiological and pathological conditions. (
  • One of the candidate targets for proton sensing is called "acid-sensing ion channels" (ASICs). (
  • Acid-Sensing Ion Channels (ASICs) are membrane protein complexes that form depolarizing ion channels present on peripheral and/or central neurons. (
  • Voiley N (2004) Acid-sensing ion channels (ASICs): new targets for the analgesic effects of non-steroid anti-inflammatory drugs (NSAIDs). (
  • Acid-sensing ion channels (ASICs) are voltage-independent, amiloride-sensitive channels involved in diverse physiological processes ranging from nociception to taste. (
  • These studies define mechanisms for activation of ASICs, illuminate the basis for dynamic ion selectivity and provide the blueprints for new therapeutic agents. (
  • Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. (
  • The results provide the first evidence that ASICs may contribute to chemotransduction of low pH by carotid body chemoreceptors, and that extracellular acidosis directly activates carotid body chemoreceptors through both ASIC and TASK channels. (
  • Acid-sensing ion channels (ASICs) are epithelial Na + channels gated by external H + . Recently, it has been demonstrated that ASICs play a role in Na + uptake in freshwater rainbow trout. (
  • ASICs are H + -gated Na + channels that belong to the epithelial Na + channel/degenerin (ENaC/DEG) superfamily (for a review, see Holzer, 2009 ). (
  • The acid-sensing ion channels (ASICs) are a family of ion channels expressed throughout the mammalian nervous system. (
  • However, not all ASICs are proton-sensitive: ASIC2a is activated by acid, whereas its splice variant ASIC2b is not. (
  • One important regulator of acid-sensing ion channels (ASICs) is zinc. (
  • Increased extracellular proton concentrations during neurotransmission are converted to excitatory sodium influx by acid-sensing ion channels (ASICs). (
  • 10-fold sodium/potassium selectivity in ASICs has long been attributed to a central constriction in the channel pore, but experimental verification is lacking due to the sensitivity of this structure to conventional manipulations. (
  • Acid-sensing ion channels (ASICs) are neuronal receptors for extracellular protons. (
  • In summary, our results show that diminazene blocks ASIC1a by a slow open-channel block and suggest that diminazene is an interesting lead compound for high-affinity blockers of ASICs. (
  • Acid-sensing ion channels (ASICs) are proton-gated cation channels that are involved in diverse neuronal processes including pain sensing. (
  • Acid-sensing (proton-gated) ion channels (ASICs): ASIC3. (
  • Acid-sensing ion channels( ASICs) are proton-gated channels expressed widely in the central nervous systems and peripheral tissues,among which ASIC1 a is a core part and plays an important role in many physiological and pathological processes. (
  • The acid-sensing ion channels (ASICs), which can be activated by acute drops in the extracellular pH, play an important role in nociception. (
  • ASICs are implicated in neurotransmission, synaptic plasticity, learning, ischaemia and neuronal cell death and contribute to perception of acid‐mediated inflammatory or post‐operative pain (Wemmie et al. (
  • Recently, the blockade of acid-sensing ion channels (ASICs) with amiloride and A-316567 attenuated the reflex. (
  • Acid-sensing ion channels (ASICs) are voltage-independent, proton-activated receptors that belong to the epithelial sodium channel/degenerin family of ion channels and are implicated in perception of pain, ischaemic stroke, mechanosensation, learning and memory. (
  • Acid sensing ion channels (ASICs) are proton-gated cation channels expressed in both central and peripheral nervous systems. (
  • In disease states, tissue acidosis is a common pathologic change causing abnormal activation of acid-sensing ion channels (ASICs), which according to cumulative evidence, significantly contributes to inflammation, mitochondrial dysfunction, and other pathologic mechanisms (i.e., pain, stroke, and psychiatric conditions). (
  • ASICs are ligand-gated cation channels activated by extracellular H + and are widely distributed in mammalian central and peripheral nervous systems. (
  • Acid-sensing ion channels (ASICs) are proton-gated Na+ channels. (
  • Acid-sensing ion channels (ASICs) are densely expressed in broad areas of mammalian brains and actively modulate synaptic transmission and a variety of neuronal activities. (
  • Little is known about the function of acid-sensing ion channels (ASICs) in bone cells or osteoporotic vertebral fractures (OVF). (
  • Acid-sensing ion channels (ASICs) are a family of ion channels comprised of six subunits encoded by four genes and they are expressed throughout the peripheral and central nervous systems. (
  • Unlike mice and humans, naked mole-rats do not perceive acid as a noxious stimulus, even though their sensory neurons express functional ASICs, likely an adaptation to living in a hypercapnic subterranean environment. (
  • Acid-sensing ion channels (ASICs) are a group of six ion channels encoded by four different genes, splice variants of the genes encoding ASIC1 and ASIC2 produce ASIC1a and ASIC1b, and ASIC2a and ASIC2b respectively [ 1 ]. (
  • Objective To study the expression and significance of acid-sensing ion channels (ASICs)in rat articular cartilage with adjuvant arthritis . (
  • Acid-sensing ion channels (ASICs) are members of the degenerin/epithelial Na + channel family of non-voltage-gated cation channels ( 1 - 3 ). (
  • These proteins (called ''acid-sensing ion channels', or ASICs) stimulate neurons when increased acid is detected. (
  • Acid- sensing ion channels (ASICs) are key sensors for extracellular protons and contribute to pain caused by tissue acidosis. (
  • In the CNS, the ASIC1A subunit is largely required for acid-evoked currents and has been implicated in synaptic plasticity, mouse models of behaviour, neurodegenerative diseases, cancer and seizures. (
  • Until now, six different isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) in rodents have been discovered and they can be assembled into homotrimers or heterotrimers to form an ion channel. (
  • The human ACCN2 gene encodes the pore-forming subunit of ASIC1a, a proton-activated, channel permeable to both Na+ and Ca2+ ions. (
  • ASIC1a channels widely expressed in the neurons of peripheral sensory and the central nervous system are therapeutic targets in pain and neurodegenerative diseases. (
  • Acid-sensing ion channel 1a (ASIC1a) is the primary acid sensor in mammalian brain and a key mediator of acidosis-induced neuronal damage following cerebral ischemia. (
  • Crystal structures of ASIC1a-psalmotoxin complexes map the toxin binding site to the extracellular domain and show how toxin binding triggers an expansion of the extracellular vestibule and stabilization of the open channel pore. (
  • Manipulating ASIC1a expression in striatal neurons in mice revealed that this channel is critical for promoting the synaptic abundance and function of NMDA receptors in response to changes in extracellular pH. (
  • By activating a kinase-dependent transcriptional program that promotes the expression of NMDA receptor subunits, ASIC1a channels stimulate synaptic activity and dendritic spine maturation in the striatal neurons that facilitate motor learning. (
  • Acid-sensing ion channel 1a (ASIC1a) is abundant in multiple brain regions, including the striatum, which serves as the input nucleus of the basal ganglia and is critically involved in procedural learning and motor memory. (
  • Acid-sensing ion channel-1a (ASIC1a) is a potential therapeutic target for multiple neurological diseases. (
  • We studied here ASIC1a glycosylation and trafficking, two poorly understood processes pivotal in determining the functional outcome of an ion channel. (
  • Inhibiting glycosylation with tunicamycin reduced ASIC1a surface trafficking, dendritic targeting, and acid-activated current density. (
  • ASIC1a glycosylation further regulates ASIC1a pH sensitivity and acid-activated current density. (
  • The Human Acid-Sensing Ion Channel ASIC1a: Evidence for a Homotetrameric Assembly State at the Cell Surface. (
  • The expression of ASIC1a monomers, trimeric or tetrameric concatemeric cDNA constructs resulted in functional channels. (
  • Our data identify a major ASIC1a homotetramer at the surface membrane of the cell expressing functional ASIC1a channel. (
  • Here, we have replaced the main chain amide carbonyl of G10' with an ester carbonyl in ASIC1a, which unlike conventional mutagenesis, allowed us to measure function in channels with alterations to the G10' main chain oxygen. (
  • Via extensive mutagenesis, further unnatural amino acid incorporation and engineered subunit stoichiometry, we established that a band of negatively charged side chains at the lower end of the channel pore enables preferential Na + conductance, revealing the molecular basis for excitatory ASIC1a function. (
  • Duan B et al (2007) Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity. (
  • Acid-sensing ion channel 1a (ASIC1a) is a primary acid sensor in the peripheral and central nervous system. (
  • Five subunits (ASIC1a, ASIC1 b, ASIC2 a, ASIC3 b and ASIC3 ) can combine to form acid-activated channels. (
  • The human ortholog of acid-sensing ion channel gene ASIC1a is associated with panic disorder and amygdala structure and function. (
  • Na + ,Ca 2+ -permeable acid-sensing ion channel 1a (ASIC1a) is involved in the pathophysiologic process of adult focal brain ischemia. (
  • External application of 1 mM Ni(2+) rapidly inhibited homomeric ASIC1a and heteromeric ASIC1a/2a channels without affecting ASIC1b, 2a, and ASIC3 homomeric channels and ASIC1a/3 and 2a/3 heteromeric channels. (
  • In contrast, external Cd(+) (1 mM) inhibited ASIC2a and ASIC3 homomeric channels and ASIC1a/2a, 1a/3, and 2a/3 heteromeric channels but not ASIC1a homomeric channels. (
  • The acid-sensing current in isolated rat hippocampus CA1 neurons, thought to be carried primarily by ASIC1a and 1a/2a, was inhibited by 1 mM Ni(2+). (
  • 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. (
  • Acid-sensing ion channel-1a (ASIC1a) is localized in brain regions with high synaptic density and is thought to contribute to synaptic plasticity, learning, and memory. (
  • The acid-sensing ion channel-1a (ASIC1a) is composed of 3 subunits and is activated by a decrease in extracellular pH. (
  • These results indicate that channel function is controlled by disulfide bond formation between intracellular residues on distinct ASIC1a subunits. (
  • Conversely, extracellular modification with a cysteine-oxidizing reagent 5,5′-dithiobis 2-nitrobenzoic acid (DTNB) decreased ASIC1a current ( 26 , 27 ). (
  • Given the signaling role of H 2 O 2 and other oxidants in normal and abnormal brain function ( 22 , 28 ) and the importance of ASIC1a in diseases associated with oxidative stress, we asked how H 2 O 2 influences ASIC1a channel structure. (
  • Why do neurons sense extracellular acid? (
  • 2002) Heteromultimers of DEG/ENaC Subunits Form H + -Gated Channels in Mouse Sensory Neurons. (
  • Mamet J, Lazdunski M, Voilley N (2003) How nerve growth factor drives physiological and inflammatory expressions of acid-sensing ion channel 3 in sensory neurons. (
  • 2001) Acid-Sensing Ion Channel 3 Matches the Acid-Gated Current in Cardiac Ischemia-Sensing Neurons. (
  • 1997a) Molecular Cloning of a Non-Inactivating Proton-Gated Na + Channel Specific for Sensory Neurons. (
  • We found that these channels can be activated in neurons of the medial nucleus of the trapezoid body (MNTB) of the auditory system in the CNS. (
  • SIGNIFICANCE STATEMENT The manuscript demonstrates that postsynaptic neurons of the medial nucleus of the trapezoid body at the mouse calyx of Held synapse express functional homomeric Acid-sensing ion channel-1a (ASIC-1as) that can be activated by protons (coreleased with neurotransmitter from acidified synaptic vesicles). (
  • Acid-sensing ion channel 1b (ASIC1b) is a proton-gated Na(+) channel mostly expressed in peripheral sensory neurons. (
  • Fu H et al (2016) Acid-sensing ion channels in trigeminal ganglion neurons innervating the orofacial region contribute to orofacial inflammatory pain. (
  • Regulation of acid signaling in rat pulmonary sensory neurons by protease-activated receptor-2. (
  • Acid-sensing ion channels (ASIC) are ligand-gated cation channels that are highly expressed in peripheral sensory and central neurons. (
  • We demonstrate here that the heavy metals Ni(2+) and Cd(2+) dose-dependently inhibit ASIC currents in hippocampus CA1 neurons and in Chinese hamster ovary (CHO) cells heterologously expressing these channels. (
  • Functional characterization of acid-sensing ion channels in cultured neurons of rat inferior colliculus. (
  • Acid-sensing ion channel 2 (ASIC2) modulates ASIC1 H+-activated currents in hippocampal neurons. (
  • Characterization of acid-sensing ion channels in dorsal horn neurons of rat spinal cord. (
  • Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action. (
  • Acid-sensing ion channels (ASIC) are members of the ENaC/Deg (epithelial amiloride-sensitive Na+ channel and degenerin) family of ion channels and are widely expressed in neurons of the central and peripheral nervous system. (
  • The Research Focus The Molecular Nociception Group focuses on genetic approaches to understanding the biology of damage-sensing neurons, somatosensation, pain and touch. (
  • Within individual neurons, it localizes to the cell soma and to dendritic spines, where it mediates an acid-activated increase in [Ca 2+ ] i and regulates spine number ( 8 - 10 ). (
  • Recent studies have demonstrated an important role for T-type Ca 2+ channels (T-channels) in controlling the excitability of peripheral pain-sensing neurons (nociceptors). (
  • After injury, peripheral pain-sensing neurons (nociceptors) can become hyperexcitable, or "sensitized. (
  • In current-clamp recording, pre-application with ET-1 (30 nM) significantly increased acid-evoked firing in rat DRG neurons. (
  • G protein-gated ion channels are a family of transmembrane ion channels in neurons and atrial myocytes that are directly gated by G proteins. (
  • G protein-gated ion channels are primarily found in CNS neurons and atrial myocytes, and affect the flow of potassium (K+), calcium (Ca2+), sodium (Na+), and chloride (Cl−) across the plasma membrane. (
  • Play media Each acid-sensing ion channel is composed of a 500-560 amino acid sequence, which is constructed into a six transmembrane segment-two per subunit (TMD1 and TMD2), a cytoplasmic amino-carboxyl termini, and a large extracellular domain. (
  • TMD1 is connected to the β-sheets of the extracellular domain that flex to widen the extracellular domain to allow for ion passage through the channel. (
  • The specific amino acid residue of aspartate on the extracellular side lumen of TMD2 in ASIC1 has been linked to the channel's low Ca2+ conductance. (
  • Distinguished by its specific amino acid configurations, the extracellular region is fundamental to the induction of activation/inactivation along with pH gating. (
  • Glycosylation is also apparent within the extracellular region, playing an important role in the trafficking the channel to the membrane's surface as well as establishing the ASIC's sensitivity to pH levels. (
  • The role of the ASIC is to sense reduced levels of extracellular pH and result in a response or signal from the neuron. (
  • The epithelial sodium channel/degenerin family encompasses a group of cation-selective ion channels that are activated or modulated by a variety of extracellular stimuli. (
  • Recent findings have begun to elucidate the structural elements that allow these channels to sense and respond to extracellular factors. (
  • This review emphasizes the roles of the extracellular domain in sensing changes in the extracellular milieu and of the residues in the extracellular-transmembrane domains interface in coupling extracellular changes to the pore of the channel. (
  • Epithelial sodium channels and acid-sensing ion channels have evolved to sense extracellular cues. (
  • These channels are opened by extracellular protons. (
  • 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. (
  • We made a series of chimeric ASIC2 proteins, and using whole-cell electrophysiology we have identified the minimal region of the ASIC2a extracellular domain that is required for ASIC2 proton activation: the first 87 amino acids after transmembrane domain 1. (
  • Changes in extracellular environment and chemical signals from adjacent cells are rapidly converted into electrical signals by ligand-gated ion channels in the cell membrane. (
  • In such acidotic states, extracellular protons provoke the pain by opening cation channels in nociceptors. (
  • The structure of ASIC1 is characterized by subunit of the chalice-shaped homotrimer that is formed by a short amino and carboxy termini, two transmembrane helices, a bound chloride ion and a disulphide-rich, multidomain extracellular region enriched in acidic residues and carboxyl-carboxylate pairs within 3.0Å, suggesting that at least one carboxyl group bears a proton. (
  • 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. (
  • Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. (
  • Here, we demonstrate that reducing agents as well as endogenous metal chelators sensitize C-type dorsal root ganglion nociceptors by chelating Zn 2+ ions off specific extracellular histidine residues on Ca v 3.2 T-channels, thus relieving tonic channel inhibition, enhancing Ca v 3.2 currents, and lowering the threshold for nociceptor excitability in vitro and in vivo . (
  • We then demonstrate that the sensitization is facilitated through a novel mechanism, whereby reducing agents chelate Zn 2+ ions off specific extracellular histidine residues in domain I of Ca v 3.2, thereby relieving tonic channel inhibition. (
  • Introduction: The acid-sensing ion channel (ASIC) is specifically activated by a drop in the extracellular pH level. (
  • One type of Cl − channel is activated by extracellular acidic pH. (
  • These ion channels, once activated, allow for the flow of potassium ions (K+) from the extracellular space surrounding the cell across the plasma membrane and into the cytoplasm. (
  • A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells. (
  • Your search returned 13 acid sensing ion channel subunit 2 ELISA ELISA Kit across 2 suppliers. (
  • Subunit-dependent high-affinity zinc inhibition of acid-sensing ion channels. (
  • ASIC2 (Acid Sensing Ion Channel Subunit 2) is a Protein Coding gene. (
  • ASIC4 (Acid Sensing Ion Channel Subunit Family Member 4) is a Protein Coding gene. (
  • Behavioral acid insensitivity is accounted for by a genetic variation in the voltage-gated Na + channel subunit 1.7 (NaV1.7), which confers enhanced acid inhibition [ 14 ]. (
  • We therefore asked if H 2 O 2 regulated their formation, where the inter-subunit links occur, and how their formation affects the channel. (
  • These four compounds (100 microM) failed to block ENaC channels expressed in oocytes. (
  • ASIC proteins are a subfamily of the ENaC/Deg superfamily of ion channels. (
  • a feature conserved in most vertebrate members of the overarching DEG/ENaC family of channels (named after invertebrate deg enerins and vertebrate e pithelial Na + c hannels). (
  • This gene encodes a member of the acid-sensing ion channel (ASIC) family of proteins, which are part of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. (
  • Acid sensing ion channels are voltage-indipendent, proton activated receptors that belong to the epithelial sodium channel (ENaC)/degenerin family of ion channels and are involved in perception of pain (and also ischaemic stroke, mechanosensation, even in learning and memory). (
  • ASIC channels belong to the ENaC/Degenerin superfamily and are proton-gated ion channels which are not voltage-dependent. (
  • and identifying a compound that alters the activity of said acid-sensing ion channel of the DEG/ENaC family that is capable of treating acidosis or excess glutamate associated with seizures or strokes, wherein said acid-sensing ion channel mediates the effects of said acidosis or excess glutamate. (
  • and detecting a change in activity of said acid-sensing ion channels of the DEG/ENaC family, thereby identifying said compound that modifies activity of said acid-sensing ion channels of the DEG/ENaC family. (
  • This gene encodes a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. (
  • This article is from PLoS ONE, volume 9.AbstractAcid-sensing ion channels Asic are ligand-gated ion channels in the Degenerin-Epithelial Na+ channel Deg-ENaC family. (
  • The function of the epithelial sodium channel, or ENaC, which helps move fluid out of air sacs normally, is even more in demand in the face of pneumonia, but the toxin impairs its ability in both the air sacs and capillaries, the scientists have now shown. (
  • They also found at work in the barrier function, a hybrid of ENaC-alpha and the acid sensing ion channel, known for its pain-mediating contributions in the brain. (
  • In mammals, acid-sensing ion channels (ASIC) are encoded by five genes that produce ASIC protein subunits: ASIC1, ASIC2, ASIC3, ASIC4, and ASIC5. (
  • The chicken acid-sensing ion channel ASIC1 has been crystallized as a homotrimer. (
  • We selected most pathways ASIC1 participated on our site, such as Inflammatory mediator regulation of TRP channels, which may be useful for your reference. (
  • ASIC1 has several biochemical functions, for example, acid-sensing ion channel activity, ion gated channel activity, ligand-gated sodium channel activity. (
  • 7, which is sufficient to activate ASIC1 a and ASIC3 channels in vitro. (
  • The neuronally expressed, proton-gated acid-sensing ion channel-1 (ASIC1) is permeable to Na+ and Ca2+, and excessive accumulation of these ions is associated with axonal degeneration. (
  • We have thus identified domains of ASIC2 that are crucial to channel function and may be important for the function of other members of the ASIC family. (
  • The outcome of this study is meaningful since it identified a new cell membrane merging mechanism of the Acid-sensing Ion Channel, and furthermore is significant that it proposed a research direction for a new understanding of the activity control mechanism of various ion channels among subunits including ASIC2, ASIC2b and many other subunits. (
  • Waldmann, R. & Lazdunski, M. H + -gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels. (
  • Acid-sensing ion channels are cation channels activated by external protons and play roles in nociception, synaptic transmission, and the physiopathology of ischemic stroke. (
  • The atomic structure of acid-sensing ion channel 1 illustrates the complex trimeric architecture of these proteins. (
  • Several metrics were collected to facilitate the analyses of the expected relationships: maximum confidence score transferred, maximum confidence score transferred from the Experiments channel in STRING, the varieties from which the relationships were transferred, and the eggNOG non-supervised orthologous organizations (NOGs) the proteins belong to. (
  • Collectively, these findings describe a novel mechanism of nociceptor sensitization and firmly establish reducing agents, as well as Zn 2+ , Zn 2+ -chelating amino acids, and Zn 2+ -chelating proteins as endogenous modulators of Ca v 3.2 and nociceptor excitability. (
  • In 2009 the use of styrene maleic acid co-polymers (SMA) for the effective extraction/solubilisation of membrane proteins was first reported [ 10 ]. (
  • Some synapses include specialized proteins that 'sense' acidity. (
  • The Iowa study shows that genetically modified mice lacking these acid-sensing proteins have a greatly reduced capacity to show either instinctive or learned fear. (
  • Ion channels are proteins composed of amino acids, the blueprint of which is coded by the genes. (
  • Generally, G protein-gated ion channels are specific ion channels located in the plasma membrane of cells that are directly activated by a family of associated proteins. (
  • A class known as metabotropic glutamate receptors play a large role in indirect ion channel activation by G proteins. (
  • They only directly activate these ion channels using effector proteins or the G protein subunits themselves (see picture). (
  • Unlike most effectors, not all G protein-gated ion channels have their activity mediated by Gα of their corresponding G proteins. (
  • These domains on the N-and C-terminal ends which interact with the G proteins contain certain residues which are critical for the proper activation of the GIRK channel. (
  • We show that inhibition of these channels using a "double-knot" spider venom peptide massively attenuates brain damage after stroke and improves behavioral outcomes, even when the peptide is administered 8 h after stroke onset. (
  • In this study, we examined the detailed zinc inhibition of ASIC1b currents and specific amino acid(s) involved in the inhibition. (
  • 2018) Inhibition of acid-sensing ion channels by diminazene and APETx2 evoke partial and highly variable antihyperalgesia in a rat model of inflammatory pain. (
  • The inhibition of potassium channels by peptides from animal venoms is a subject of broad interest for its physiological and therapeutic applications [ 1 ]. (
  • Certain peptides even lead to clinical development and venom-based drugs, such as ziconotide, which is an inhibitor of neuronal voltage-gated calcium channels isolated from Conus magus , designed for patients with intra-ctable pain who fail to respond to other drugs [ 57 , 66 ]. (
  • 1997) BNaC1 and BNaC2 Constitute a New Family of Human Neuronal Sodium Channels Related to Degenerins and Epithelial Sodium Channels. (
  • Members of the ASIC family of acid-sensing ion channels are abundant in various regions of the brain and mediate neuronal synaptic function. (
  • A family of proton-gated sodium channels that are primarily expressed in neuronal tissue. (
  • 1. Baron A, Lingueglia E. (2015) Pharmacology of acid-sensing ion channels - Physiological and therapeutical perspectives. (
  • Acid-sensing ion channels are broadly distributed in the nervous system where they contribute to the sensory processes. (
  • 1998) A Sensory Neuron-Specific, Proton-Gated Ion Channel. (
  • 2002) Proinflammatory Mediators, Stimulators of Sensory Neuron Excitability Via the Expression of Acid-Sensing Ion Channels. (
  • Lingueglia E (2007) Acid-sensing ion channels in sensory perception. (
  • 5. Mamet J, Baron A, Lazdunski M, Voilley N. (2002) Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels. (
  • These channels are sensitive to changes in pH and are expressed throughout the central and peripheral nervous systems-including brain, spinal cord, and sensory ganglia. (
  • The researchers therefore investigated the function of this ion channel in naked mole-rat and in mouse sensory nerves to determine whether there is a difference between the two species in the function of this ion channel. (
  • Three of these protein subunits assemble to form the ASIC, which can combine into both homotrimeric and heterotrimeric channels typically found in both the central nervous system and peripheral nervous system. (
  • However, the gating and mechanics of each acid-sensing ion channel is determined by the combination of ASIC subunits that form its structure. (
  • 6, and the combination of different subunits can produce properties different from those of homomeric channels. (
  • pH Dependency and desensitization kinetics of heterologously expressed combinations of acid-sensing ion channel subunits. (
  • This acidic pocket contains several pairs of acidic amino acids, is situated at the interface between two subunits, and is considered one of the ASIC pH sensors. (
  • These subunits form functional ion channels as dimers or heteropolymers, and differing channels vary in activation conditions, ion selectivity, kinetics, and distributions. (
  • The research team identified through animal experiments that there is a different cell membrane merging mechanism between subunits of the Acid-sensing Ion Channel. (
  • A trimer of subunits comprises the channel ( 4 ), which can be composed of homologous or heterologous subunits. (
  • These three altered protein subunits lead to profound impairment or blockage of the naked mole-rat ion channel by acid. (
  • Four G protein gated inwardly-rectifying potassium (GIRK) channel subunits have been identified in mammals: GIRK1, GIRK2, GIRK3, and GIRK4. (
  • The GIRK subunits come together to form GIRK ion channels. (
  • Because of their similarity, the GIRK channel subunits can come together easily to form heteromultimers (a protein with two or more different polypeptide chains). (
  • Though GIRK3 subunits are found in the CNS, their role in forming functional ion channels is still unknown. (
  • Sustained currents through ASIC3 ion channels at the modest pH changes that occur during myocardial ischemia. (
  • Homozygous Asic3 (amiloride-sensitive cation channel 3) targeted mutation mice display alterations in normal and pain-associated cutaneous mechanosensitivity and inflammatory pain sensation, visual loss associated with night blindness, and age-induced hearing loss. (
  • However, the sustained depolarization was not blocked by amiloride but was eliminated by removal of K + from the pipette solution which reduced significantly intracellular K + . This sustained depolarization was partially blocked by the TASK channels blockers anandamide (from 14.9±1.6 mV to 9.3±2.2 mV at pH 6.0, n=5) and quinidine (from 27.5±2.2 mV to 11.3±2.3 mV at pH 6.0, n=3). (
  • Monoamine NMDA receptor channel blockers inhibit and potentiate native and recombinant proton-gated ion channels. (
  • Common binding site for externally and internally applied AMPA receptor channel blockers. (
  • Organic blockers escape from trapping in the AMPA receptor channels by leaking into the cytoplasm. (
  • Effects of ionotropic glutamate receptor channel blockers on the development of pentylenetetrazol kindling in mice. (
  • A subclass of sodium channel blockers that are specific for ACID-SENSING SODIUM CHANNELS. (
  • Dentists already use sodium ion channel blockers in the form of local anesthetics, but these target all sodium ion channels they come into contact with, not just the Nav1.7 ion channel. (
  • Cation channel that gives rise to very low constitutive currents in the absence of activation. (
  • a phenomenon that adds to the functional diversity of acid-mediated currents. (
  • In whole-cell voltage-clamp recording, ASIC currents were evoked by brief local application of pH 6.0 external solution in the presence of TRPV1 channel blocker AMG9810. (
  • The acid- or proton-activated Cl − (PAC) currents are present in a wide range of mammalian cells ( 2 ). (
  • This gene belongs to the superfamily of acid-sensing ion channels, which are proton-gated, amiloride-sensitive sodium channels. (
  • Histamine selectively potentiates acid-sensing ion channel 1a. (
  • ASIC4 has several biochemical functions, for example, ion channel activity, sodium channel activity, sodium ion transmembrane transporter activity. (
  • A disulphide-rich "tumb" domain is between the acidic residues and the transmembrane pore: it may couple the binding of protons to the opening of the ion channel. (
  • The protein, called PAC for proton-activated channel, has two predicted transmembrane domains and is unlike any previously identified channel. (
  • These ion channels are transmembrane ion channels with selectivity filters and a G protein binding site. (
  • proteolytic cleavage of human acid-sensing ion channel 1 [ PMID: 20601429 ] and the regulation of the matriptase-prostasin cell surface proteolytic cascade by hepatocyte growth factor activator inhibitor-1 during epidermal differentiation [ PMID: 20696767 ]. (
  • The intracellular amino-carboxyl termini domains are vital to the channel's intracellular protein interactions and modulations, ion permeability, and gating. (
  • TMD2 is primarily involved with lining of the lumen within the pore and inactivation gate of the channel, where as TMD1 holds the protein within the cell's lipid bilayer. (
  • 2002) Protein Kinase C Stimulates the Acid-Sensing Ion Channel ASIC2a Via the PDZ Domain-Containing Protein PICK1. (
  • In the twelve years since styrene maleic acid (SMA) was first used to extract and purify a membrane protein within a native lipid bilayer, this technological breakthrough has provided insight into the structural and functional details of protein-lipid interactions. (
  • Several of the experiments described in the Iowa paper showed that inhaling elevated concentrations of carbon dioxide triggered strong fear reactions in normal mice, and that some of these fear reactions required the presence of the acid-sensing protein in the amygdala. (
  • used an unbiased RNA interference screen to identify the channel protein that allows such proton-activated ion conductance. (
  • G protein-gated ion channels are associated with a specific type of G protein-coupled receptor. (
  • The GPCRs associated with G protein-gated ion channels are not involved in signal transduction pathways. (
  • These domains interact directly with the βγ-complex of the G protein, leading to activation of the K+ channel. (
  • Potent neuroprotection after stroke afforded by a double-knot spider toxin that inhibits acid-sensing ion channel 1a. (
  • This mutant mouse line contains a transgene that consists of a hemagglutnin-tagged mouse Accn3 (amiloride-sensitive cation channel 3)cDNA driven by the rat Syn1 (synapsin1) promoter. (
  • Peptides inhibitors of acid-sensing ion channels. (
  • Dual signaling of Wamide myoinhibitory peptides through a peptide-gated channel and a GPCR in Platynereis. (
  • To explore structure-function, gating mechanisms and tissue localization of many ion channels, animal venom toxins were important pharmacological tools in the ion channel field [ 28 ]. (
  • This review describes findings that provide new insights into the molecular mechanisms that control the function of these channels. (
  • However, despite considerable research efforts, the mechanisms of ion acquisition and identity of the transporters involved in ion uptake in fresh water are still not fully understood. (
  • Modulation of acid-sensing ion channels: molecular mechanisms and therapeutic potential. (
  • Discovery of the ASIC crystal structure provided insight into inherent mechanisms of channel depolarization, inactivation, and modulation. (
  • Professor Suh's 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. (
  • Mechanisms of the blockade of glutamate channel receptors: significance for structural and physiological investigations. (
  • However, the molecular mechanisms underlying the functions of T-channels in nociceptors are poorly understood. (
  • However, the molecular mechanisms of the cellular response to acid are not fully understood. (
  • The combination of the structural and physiological data indicates that Mamba1 prefers to bind hASIC1a in a closed state and reduces the proton sensitivity of the channel, representing a closed-state trapping mechanism. (
  • Venom toxins in the exploration of molecular, physiological and pathophysiological functions of acid-sensing ion channels. (
  • Exposure of cells to acidic conditions outside the cell activates chloride-conducting channels that influence physiological and pathological processes. (
  • Identification of the channel should advance studies of its physiological roles, which range from tissue injury after stroke to adaptation of Tibetan natives to a high-altitude environment. (
  • The wide expression of PAC suggests a broad role for this conserved Cl − channel family in physiological and pathological processes associated with acidic pH. (
  • Diarylamidines: high potency inhibitors of acid-sensing ion channels. (
  • MacDonald, John F. / Diarylamidines : High potency inhibitors of acid-sensing ion channels . (
  • Sea anemones are a rich source of two classes of peptide toxins, sodium channel toxins and potassium channel toxins, which have been or will be useful tools for studying the structure and function of specific ion channels. (
  • Of the three classes of toxins, both sodium and potassium channel peptide toxins have been useful tools for studying the structure and function of ion channels, because of their high affinity to the specific channel. (
  • 1975 ), more than 50 sodium channel peptide toxins have been isolated and/or cloned from various species of sea anemones. (
  • We also provided more evidence that targeting these channels with the TIP peptide or something similar is a solid strategy for reducing dangerous fluid volume in your lungs," says Lucas. (
  • ASIC2b is non-functional on its own but modulates channel activity when participating in heteromultimers and ASIC4 has no known function. (
  • Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system. (
  • Kühn, F.J.P. Ehrlich, W. Barth, D. Kühn, C. Lückhoff, A. Functional importance of NUDT9H domain and N-terminal ADPR-binding pocket in two species variants of vertebrate TRPM2 channels. (
  • The activated channel exhibits selectivity for sodium, and is inhibited by amiloride. (
  • At pH 7.25 the pore is approximately 10 Å in diameter, whereas at pH 5.5 the pore is largely hydrophobic and elliptical in cross-section with dimensions of approximately 5 by 7 Å, consistent with a barrier mechanism for ion selectivity. (
  • Here, we explored the basis for ion selectivity by incorporating unnatural amino acids into the channel, engineering channel stoichiometry and performing free energy simulations. (
  • Thus, the molecular determinants of ion selectivity and in turn the basis for excitatory function in this family of ligand-gated ion channel remains an open question. (
  • Both approaches support the conclusion that other parts of the pore contribute more markedly to ion selectivity than the GAS belt. (
  • BDS-I and II, which show selectivity for Kv3.4 channels and APETx1, which inhibits human ether-a-go-go -related gene potassium channels. (
  • These residues form an acidic pocket that express electrostatic potentials that are responsible for pH-dependency in channel activation and modulation. (
  • Muscarinic M1 modulation of acid-sensing ion channels. (
  • Collectively, our data further support a role for Ca v 3.2 channels in peripheral nociception and identify a novel mechanism for Ca v 3.2 modulation that underlies nociceptor sensitization. (
  • AUGUSTA, Ga. (Sept. 5, 2017) - Sodium channels in the cells that line the tiny capillaries in our lungs play an important role in keeping those capillaries from leaking and potentially worsening conditions like pneumonia, scientists report. (
  • Gene Ontology (GO) annotations related to this gene include ion channel activity and voltage-gated sodium channel activity . (
  • Our group combines recombinant DNA technology, electrophysiology, in vivo imaging, gene targeting and behavioural approaches to explore the channels, receptors, transcription factors and regulatory pathways that control nociceptor excitability. (
  • In a number of mammals the structure of the gene for the Nav1.7 ion channel has been decoded. (
  • The overall goal of the experiments proposed in this application is to shed light on the role played by lactic acid in evoking the exercise pressor reflex in both health and simulated peripheral artery disease. (
  • Price, M. P., Snyder, P. M. & Welsh, M. J. Cloning and expression of a novel human brain Na + channel. (
  • Acid-sensing Ion Channels Activation and Hypoxia Upregulate Homer1a Expression. (
  • 2001) Nonsteroid Anti-Inflammatory Drugs Inhibit Both the Activity and the Inflammation-Induced Expression of Acid-Sensing Ion Channels in Nociceptors. (
  • 1. Voilley N, de Weille J, Mamet J, Lazdunski M. (2001) Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. (
  • Their expression within areas of interest in the brain in migraine, such as the hypothalamus and PAG, their demonstrated involvement in preclinical models of meningeal afferent signaling, and their role in cortical spreading depression (the electrophysiological correlate of migraine aura), has enhanced research interest into these channels as potential therapeutic targets in migraine. (
  • Vol 9: Restrictive Expression of Acid-Sensing Ion Channel 5 Asic5 in Unipolar Brush Cells of the Vestibulocerebellum. (
  • Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking of ASIC2b via Heteromeric Assembly', Scientific Reports 2016. (
  • Even the earliest papers describing H+-activated channels recognized that the channels might function as nociceptors. (
  • Sensitivity of mechanoreceptors responding to noxious pinch is decreased as is the response of acid- and noxious heat-sensitive nociceptors. (
  • These observations led to the hypothesis that ASIC s, and possibly other acid-activated receptors, have a critical role in nociception, but how ASIC s transduce or modulate painful stimuli has not been established yet. (
  • In particular, this invention relates to pharmaceutical compositions, dietary supplements and methods of treatment which modulate the acid-sensing ion channel (ASIC) for treatment of Central Nervous System (CNS) disorders such as seizures and strokes through synaptic plasticity, treatment of cognitive disorders, and for memory enhancement. (
  • Heteromeric channel assembly seems to modulate. (
  • Ligands of histamine receptors modulate acid-sensing ion channels. (
  • These channels have been implicated in synaptic transmission, pain perception as well as mechanoperception. (
  • We now know that they contribute to synaptic transmission at excitatory synapses as well as to sensing metabolic acidosis and nociception. (
  • Acid Sensing Ion Channels" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (
  • Amino acid sequences of soidum channel toxins from sea anemones. (
  • In the NaV1.7 ion channel of the naked mole-rat, three amino acid building blocks are different from those in all other mammals. (
  • The precipitous drop in brain pH resulting from stroke activates acid-sensing ion channel 1a. (
  • In body tissues, CO2 is converted into acid, which continuously activates pain sensors. (
  • However, it remains fairly inconclusive of which particular residues interact with protons to activate the channel. (
  • These high acid levels in the tissue activate the pain sensors. (
  • This is also the case when in the nerve cells of the naked mole-rats other ion channels are activated by acid stimuli that would normally activate pain receptors. (
  • A troubled lung also becomes acidic, which can activate this acid sensing ion channel. (
  • 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. (
  • Proteolytic cleavage of human acid-sensing ion channel 1 by the serine protease matriptase. (
  • Divalent cation and chloride ion sites of chicken acid sensing ion channel 1a elucidated by x-ray crystallography. (
  • Finally, we identify by molecular docking a binding site in the ion pore that we confirm by site-directed mutagenesis. (
  • Each channel consists of domains which span the plasma membrane, forming the K+-selective pore region through which the K+ ions will flow. (
  • Acid-sensitive ion channels and receptors. (
  • However, naked mole-rats are an exception: they have an altered ion channel in their pain receptors that is inactivated by acid and makes the animals insensitive to this type of pain. (
  • Identification of aurintricarboxylic acid as a potent allosteric antagonist of P2X1 and P2X3 receptors. (
  • 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. (
  • Although the threshold to elicit I Cl,H is relatively low, ~pH 5.5 at room temperature (RT), the channels become activated under less acidic conditions of ~pH 6.0 at 37°C ( 3 , 4 ). (
  • Venoms of species like spiders, sea anemones and snakes have been found to target ion channels with highly therapeutic potentials as drug candidates [ 17 , 38 ]. (
  • Acid-sensing ion channels: advances, questions and therapeutic opportunities. (
  • The findings are expected to have a significant impact on further studies focusing on the development of therapeutic agents that control pain by providing a more precise understanding of the operational mechanism of the 'Acid-sensing Ion Channel' that plays a pivotal role in transmitting pain signals. (
  • Sodium Channels in Pain and Cancer: New Therapeutic Opportunities. (
  • It is generally believed that a vanilloid receptor subtype-1 (VR1) and an acid-sensing ion channel (ASIC) mediate the greater part of acid-induced nociception in mammals. (

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