Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.Ion Channel Gating: The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.Acid Sensing Ion Channels: A family of proton-gated sodium channels that are primarily expressed in neuronal tissue. They are AMILORIDE-sensitive and are implicated in the signaling of a variety of neurological stimuli, most notably that of pain in response to acidic conditions.Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.Potassium Channels, Inwardly Rectifying: Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.Chloride Channels: Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.Potassium Channel Blockers: A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Potassium Channels, Voltage-Gated: Potassium channel whose permeability to ions is extremely sensitive to the transmembrane potential difference. The opening of these channels is induced by the membrane depolarization of the ACTION POTENTIAL.Ligand-Gated Ion Channels: A subclass of ion channels that open or close in response to the binding of specific LIGANDS.Calcium Channels, L-Type: Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.Potassium Channels, Calcium-Activated: Potassium channels whose activation is dependent on intracellular calcium concentrations.KATP Channels: Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Shaker Superfamily of Potassium Channels: Voltage-gated potassium channels whose primary subunits contain six transmembrane segments and form tetramers to create a pore with a voltage sensor. They are related to their founding member, shaker protein, Drosophila.Cyclic Nucleotide-Gated Cation Channels: A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore-loop cation channels. They are expressed in OLFACTORY NERVE cilia and in PHOTORECEPTOR CELLS and some PLANTS.Sodium Channel Blockers: A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).TRPC Cation Channels: A subgroup of TRP cation channels that contain 3-4 ANKYRIN REPEAT DOMAINS and a conserved C-terminal domain. Members are highly expressed in the CENTRAL NERVOUS SYSTEM. Selectivity for calcium over sodium ranges from 0.5 to 10.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Large-Conductance Calcium-Activated Potassium Channels: A major class of calcium activated potassium channels whose members are voltage-dependent. MaxiK channels are activated by either membrane depolarization or an increase in intracellular Ca(2+). They are key regulators of calcium and electrical signaling in a variety of tissues.TRPM Cation Channels: A subgroup of TRP cation channels named after melastatin protein. They have the TRP domain but lack ANKYRIN repeats. Enzyme domains in the C-terminus leads to them being called chanzymes.Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active, passive or facilitated. Ions may travel by themselves (uniport), or as a group of two or more ions in the same (symport) or opposite (antiport) directions.Xenopus laevis: The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.TRPV Cation Channels: A subgroup of TRP cation channels named after vanilloid receptor. They are very sensitive to TEMPERATURE and hot spicy food and CAPSAICIN. They have the TRP domain and ANKYRIN repeats. Selectivity for CALCIUM over SODIUM ranges from 3 to 100 fold.Calcium Channels, N-Type: CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.Oocytes: Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).Calcium Channels, T-Type: A heterogenous group of transient or low voltage activated type CALCIUM CHANNELS. They are found in cardiac myocyte membranes, the sinoatrial node, Purkinje cells of the heart and the central nervous system.Kv1.2 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.Epithelial Sodium Channels: Sodium channels found on salt-reabsorbing EPITHELIAL CELLS that line the distal NEPHRON; the distal COLON; SALIVARY DUCTS; SWEAT GLANDS; and the LUNG. They are AMILORIDE-sensitive and play a critical role in the control of sodium balance, BLOOD VOLUME, and BLOOD PRESSURE.Transient Receptor Potential Channels: A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN repeats are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES.Ether-A-Go-Go Potassium Channels: A family of voltage-gated potassium channels that are characterized by long N-terminal and C-terminal intracellular tails. They are named from the Drosophila protein whose mutation causes abnormal leg shaking under ether anesthesia. Their activation kinetics are dependent on extracellular MAGNESIUM and PROTON concentration.Potassium: An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.Kv1.3 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Kv1.1 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.Kv1.5 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that conducts a delayed rectifier current. It contributes to ACTION POTENTIAL repolarization of MYOCYTES in HEART ATRIA.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Kinetics: The rate dynamics in chemical or physical systems.KCNQ1 Potassium Channel: A voltage-gated potassium channel that is expressed primarily in the HEART.KCNQ Potassium Channels: A family of delayed rectifier voltage-gated potassium channels that share homology with their founding member, KCNQ1 PROTEIN. KCNQ potassium channels have been implicated in a variety of diseases including LONG QT SYNDROME; DEAFNESS; and EPILEPSY.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Calcium Channel Agonists: Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.Shab Potassium Channels: A subfamily of shaker potassium channels that shares homology with its founding member, Shab protein, Drosophila. They regulate delayed rectifier currents in the NERVOUS SYSTEM of DROSOPHILA and in the SKELETAL MUSCLE and HEART of VERTEBRATES.Sodium Channels: Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.Kv1.4 Potassium Channel: A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: A subgroup of cyclic nucleotide-regulated ION CHANNELS of the superfamily of pore-loop cation channels that are opened by hyperpolarization rather than depolarization. The ion conducting pore passes SODIUM, CALCIUM, and POTASSIUM cations with a preference for potassium.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Small-Conductance Calcium-Activated Potassium Channels: A major class of calcium-activated potassium channels that are found primarily in excitable CELLS. They play important roles in the transmission of ACTION POTENTIALS and generate a long-lasting hyperpolarization known as the slow afterhyperpolarization.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Cations: Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.Shaw Potassium Channels: A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.Shal Potassium Channels: A shaker subfamily of potassium channels that participate in transient outward potassium currents by activating at subthreshold MEMBRANE POTENTIALS, inactivating rapidly, and recovering from inactivation quickly.Protein Subunits: Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Degenerin Sodium Channels: A family of mechanosensitive sodium channels found primarily in NEMATODES where they play a role in CELLULAR MECHANOTRANSDUCTION. Degenerin sodium channels are structurally-related to EPITHELIAL SODIUM CHANNELS and are named after the fact that loss of their activity results in cellular degeneration.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as CATIONS; those with a negative charge are ANIONS.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.NAV1.5 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of CARDIOMYOCYTES. Defects in the SCN5A gene, which codes for the alpha subunit of this sodium channel, are associated with a variety of CARDIAC DISEASES that result from loss of sodium channel function.G Protein-Coupled Inwardly-Rectifying Potassium Channels: A family of inwardly-rectifying potassium channels that are activated by PERTUSSIS TOXIN sensitive G-PROTEIN-COUPLED RECEPTORS. GIRK potassium channels are primarily activated by the complex of GTP-BINDING PROTEIN BETA SUBUNITS and GTP-BINDING PROTEIN GAMMA SUBUNITS.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Acid Sensing Ion Channel Blockers: A subclass of sodium channel blockers that are specific for ACID-SENSING SODIUM CHANNELS.Potassium Channels: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.Gramicidin: A group of peptide antibiotics from BACILLUS brevis. Gramicidin C or S is a cyclic, ten-amino acid polypeptide and gramicidins A, B, D are linear. Gramicidin is one of the two principal components of TYROTHRICIN.Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous.KCNQ2 Potassium Channel: A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Chlorides: Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.Scorpion Venoms: Venoms from animals of the order Scorpionida of the class Arachnida. They contain neuro- and hemotoxins, enzymes, and various other factors that may release acetylcholine and catecholamines from nerve endings. Of the several protein toxins that have been characterized, most are immunogenic.Tetraethylammonium: A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)Intermediate-Conductance Calcium-Activated Potassium Channels: A major class of calcium-activated potassium channels that were originally discovered in ERYTHROCYTES. They are found primarily in non-excitable CELLS and set up electrical gradients for PASSIVE ION TRANSPORT.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Ryanodine Receptor Calcium Release Channel: A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.Biophysics: The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.Delayed Rectifier Potassium Channels: A group of slow opening and closing voltage-gated potassium channels. Because of their delayed activation kinetics they play an important role in controlling ACTION POTENTIAL duration.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Large-Conductance Calcium-Activated Potassium Channel alpha Subunits: The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Nerve Tissue ProteinsKCNQ3 Potassium Channel: A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is closely related to KCNQ2 POTASSIUM CHANNEL. It is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.Voltage-Gated Sodium Channels: A family of membrane proteins that selectively conduct SODIUM ions due to changes in the TRANSMEMBRANE POTENTIAL DIFFERENCE. They typically have a multimeric structure with a core alpha subunit that defines the sodium channel subtype and several beta subunits that modulate sodium channel activity.NAV1.2 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that mediates the sodium ion permeability of excitable membranes. Defects in the SCN2A gene which codes for the alpha subunit of this sodium channel are associated with benign familial infantile seizures type 3, and early infantile epileptic encephalopathy type 11.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Calcium Channels, P-Type: CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.Biophysical Phenomena: The physical characteristics and processes of biological systems.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.Receptors, Nicotinic: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.Amiloride: A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)Charybdotoxin: A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Alamethicin: A cyclic nonadecapeptide antibiotic that can act as an ionophore and is produced by strains of Trichoderma viride. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Calcium Channels, R-Type: CALCIUM CHANNELS located in the neurons of the brain. They are inhibited by the marine snail toxin, omega conotoxin MVIIC.Sodium Channel Agonists: A class of drugs that stimulate sodium influx through cell membrane channels.Calcium Channels, Q-Type: CALCIUM CHANNELS located in the neurons of the brain.Voltage-Dependent Anion Channels: A family of voltage-gated eukaryotic porins that form aqueous channels. They play an essential role in mitochondrial CELL MEMBRANE PERMEABILITY, are often regulated by BCL-2 PROTO-ONCOGENE PROTEINS, and have been implicated in APOPTOSIS.Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Mechanotransduction, Cellular: The process by which cells convert mechanical stimuli into a chemical response. It can occur in both cells specialized for sensing mechanical cues such as MECHANORECEPTORS, and in parenchymal cells whose primary function is not mechanosensory.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Tetrodotoxin: An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Electrophysiological Phenomena: The electrical properties, characteristics of living organisms, and the processes of organisms or their parts that are involved in generating and responding to electrical charges.Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Sulfonylurea Receptors: ATP-BINDING CASSETTE PROTEINS that are highly conserved and widely expressed in nature. They form an integral part of the ATP-sensitive potassium channel complex which has two intracellular nucleotide folds that bind to sulfonylureas and their analogs.Receptors, Purinergic P2X2: A purinergic P2X neurotransmitter receptor involved in sensory signaling of TASTE PERCEPTION, chemoreception, visceral distension and NEUROPATHIC PAIN. The receptor comprises three P2X2 subunits. The P2X2 subunits also have been found associated with P2X3 RECEPTOR subunits in a heterotrimeric receptor variant.Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Receptors, Drug: Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.Recombinant Proteins: Proteins prepared by recombinant DNA technology.4-Aminopyridine: One of the POTASSIUM CHANNEL BLOCKERS, with secondary effect on calcium currents, which is used mainly as a research tool and to characterize channel subtypes.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Channelopathies: A variety of neuromuscular conditions resulting from MUTATIONS in ION CHANNELS manifesting as episodes of EPILEPSY; HEADACHE DISORDERS; and DYSKINESIAS.Heavy Ions: Positively-charged atomic nuclei that have been stripped of their electrons. These particles have one or more units of electric charge and a mass exceeding that of the Helium-4 nucleus (alpha particle).Cesium: A member of the alkali metals. It has an atomic symbol Cs, atomic number 50, and atomic weight 132.91. Cesium has many industrial applications, including the construction of atomic clocks based on its atomic vibrational frequency.NAV1.4 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of SKELETAL MYOCYTES. Defects in the SCN4A gene, which codes for the alpha subunit of this sodium channel, are associated with several MYOTONIC DISORDERS.Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.Receptors, Serotonin, 5-HT3: A subclass of serotonin receptors that form cation channels and mediate signal transduction by depolarizing the cell membrane. The cation channels are formed from 5 receptor subunits. When stimulated the receptors allow the selective passage of SODIUM; POTASSIUM; and CALCIUM.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Dihydropyridines: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.Ion Pumps: A general class of integral membrane proteins that transport ions across a membrane against an electrochemical gradient.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Receptors, Glycine: Cell surface receptors that bind GLYCINE with high affinity and trigger intracellular changes which influence the behavior of cells. Glycine receptors in the CENTRAL NERVOUS SYSTEM have an intrinsic chloride channel and are usually inhibitory.Ganglia, Spinal: Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain.Myocytes, Cardiac: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.NAV1.8 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that is expressed in nociceptors, including spinal and trigeminal sensory neurons. It plays a role in the transmission of pain signals induced by cold, heat, and mechanical stimuli.Apamin: A highly neurotoxic polypeptide from the venom of the honey bee (Apis mellifera). It consists of 18 amino acids with two disulfide bridges and causes hyperexcitability resulting in convulsions and respiratory paralysis.Cations, Monovalent: Positively charged atoms, radicals or group of atoms with a valence of plus 1, which travel to the cathode or negative pole during electrolysis.Receptors, Purinergic P2X: A subclass of purinergic P2 receptors that signal by means of a ligand-gated ion channel. They are comprised of three P2X subunits which can be identical (homotrimeric form) or dissimilar (heterotrimeric form).Permeability: Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.RNA, Complementary: Synthetic transcripts of a specific DNA molecule or fragment, made by an in vitro transcription system. This cRNA can be labeled with radioactive uracil and then used as a probe. (King & Stansfield, A Dictionary of Genetics, 4th ed)Tetraethylammonium Compoundsomega-Conotoxin GVIA: A neurotoxic peptide, which is a cleavage product (VIa) of the omega-Conotoxin precursor protein contained in venom from the marine snail, CONUS geographus. It is an antagonist of CALCIUM CHANNELS, N-TYPE.Heart: The hollow, muscular organ that maintains the circulation of the blood.Large-Conductance Calcium-Activated Potassium Channel beta Subunits: The regulatory subunits of large-conductance calcium-activated potassium channels.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Long QT Syndrome: A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.Saxitoxin: A compound that contains a reduced purine ring system but is not biosynthetically related to the purine alkaloids. It is a poison found in certain edible mollusks at certain times; elaborated by GONYAULAX and consumed by mollusks, fishes, etc. without ill effects. It is neurotoxic and causes RESPIRATORY PARALYSIS and other effects in MAMMALS, known as paralytic SHELLFISH poisoning.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Cricetulus: A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.Torpedo: A genus of the Torpedinidae family consisting of several species. Members of this family have powerful electric organs and are commonly called electric rays.Water: A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Quaternary Ammonium Compounds: Derivatives of ammonium compounds, NH4+ Y-, in which all four of the hydrogens bonded to nitrogen have been replaced with hydrocarbyl groups. These are distinguished from IMINES which are RN=CR2.Cystic Fibrosis Transmembrane Conductance Regulator: A chloride channel that regulates secretion in many exocrine tissues. Abnormalities in the CFTR gene have been shown to cause cystic fibrosis. (Hum Genet 1994;93(4):364-8)Receptors, Purinergic P2: A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.Mesylates: Organic salts or esters of methanesulfonic acid.Phosphatidylinositol 4,5-Diphosphate: A phosphoinositide present in all eukaryotic cells, particularly in the plasma membrane. It is the major substrate for receptor-stimulated phosphoinositidase C, with the consequent formation of inositol 1,4,5-triphosphate and diacylglycerol, and probably also for receptor-stimulated inositol phospholipid 3-kinase. (Kendrew, The Encyclopedia of Molecular Biology, 1994)Porosity: Condition of having pores or open spaces. This often refers to bones, bone implants, or bone cements, but can refer to the porous state of any solid substance.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Sensory Receptor Cells: Specialized afferent neurons capable of transducing sensory stimuli into NERVE IMPULSES to be transmitted to the CENTRAL NERVOUS SYSTEM. Sometimes sensory receptors for external stimuli are called exteroceptors; for internal stimuli are called interoceptors and proprioceptors.Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Static Electricity: The accumulation of an electric charge on a objectMechanoreceptors: Cells specialized to transduce mechanical stimuli and relay that information centrally in the nervous system. Mechanoreceptor cells include the INNER EAR hair cells, which mediate hearing and balance, and the various somatosensory receptors, often with non-neural accessory structures.Pinacidil: A guanidine that opens POTASSIUM CHANNELS producing direct peripheral vasodilatation of the ARTERIOLES. It reduces BLOOD PRESSURE and peripheral resistance and produces fluid retention. (Martindale The Extra Pharmacopoeia, 31st ed)Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Neurons, Afferent: Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM.Sarcolemma: The excitable plasma membrane of a muscle cell. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Spider Venoms: Venoms of arthropods of the order Araneida of the ARACHNIDA. The venoms usually contain several protein fractions, including ENZYMES, hemolytic, neurolytic, and other TOXINS, BIOLOGICAL.Batrachotoxins: Batrachotoxin is the 20-alpha-bromobenzoate of batrachotoxin A; they are toxins from the venom of a small Colombian frog, Phyllobates aurotaenia, cause release of acetylcholine, destruction of synaptic vesicles and depolarization of nerve and muscle fibers.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Conotoxins: Peptide neurotoxins from the marine fish-hunting snails of the genus CONUS. They contain 13 to 29 amino acids which are strongly basic and are highly cross-linked by disulfide bonds. There are three types of conotoxins, omega-, alpha-, and mu-. OMEGA-CONOTOXINS inhibit voltage-activated entry of calcium into the presynaptic membrane and therefore the release of ACETYLCHOLINE. Alpha-conotoxins inhibit the postsynaptic acetylcholine receptor. Mu-conotoxins prevent the generation of muscle action potentials. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)Mibefradil: A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE.Cation Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of positively charged molecules (cations) across a biological membrane.Receptors, Cholinergic: Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.omega-Conotoxins: A family of structurally related neurotoxic peptides from mollusk venom that inhibit voltage-activated entry of calcium into the presynaptic membrane. They selectively inhibit N-, P-, and Q-type calcium channels.Receptors, Purinergic P2X4: A widely distributed purinergic P2X receptor subtype that plays a role in pain sensation. P2X4 receptors found on MICROGLIA cells may also play a role in the mediation of allodynia-related NEUROPATHIC PAIN.Electrochemistry: The study of chemical changes resulting from electrical action and electrical activity resulting from chemical changes.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Nitrobenzoates: Benzoic acid or benzoic acid esters substituted with one or more nitro groups.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Connexins: A group of homologous proteins which form the intermembrane channels of GAP JUNCTIONS. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions.NAV1.1 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that is predominantly expressed in the CENTRAL NERVOUS SYSTEM. Defects in the SCN1A gene which codes for the alpha subunit of this sodium channel are associated with DRAVET SYNDROME, generalized epilepsy with febrile seizures plus, type 2 (GEFS+2), and familial hemiplegic migraine type 3.Aquaporins: A class of porins that allow the passage of WATER and other small molecules across CELL MEMBRANES.

Intracellular sodium modulates the expression of angiotensin II subtype 2 receptor in PC12W cells. (1/10550)

Although the angiotensin II subtype 2 receptor (AT2-R) is expressed abundantly in the adrenal medulla, its physiological significance has not yet been determined. To obtain fundamental knowledge of the regulation of AT2-R expression in the adrenal medulla, we investigated the effects of modulating several ion channels on AT2-R expression in PC12W cells. Experiments were performed after 24 hours of serum depletion under subconfluent conditions. After 48 hours of treatment with various agonists or antagonists, the receptor density and mRNA level of AT2-Rs were quantified by 125I-[Sar1, Ile8]angiotensin II binding and Northern blot analysis. Ouabain (10 to 100 nmol/L) and insulin (10 to 100 nmol/L) dose-dependently increased receptor density and mRNA level. Analysis of the binding characteristics revealed that the ouabain-dependent increase in AT2-R levels was due to an increase in binding capacity without a change in the Kd value. These increases were blocked by lowering the Na+ concentration in the medium. A low concentration of the sodium ionophore monensin (10 nmol/L), the K+-channel blocker quinidine (10 micromol/L), and the ATP-sensitive K+-channel blockers tolbutamide (100 micromol/L) and glybenclamide (10 micromol/L) also significantly increased receptor density, but the ATP-sensitive K+-channel agonist cromakalim (100 micromol/L) decreased receptor density significantly (P<0.01). Nifedipine (10 micromol/L) decreased basal receptor density and completely blocked the increase in receptor density caused by these agents. The increase in receptor density caused by an increase in intracellular Na+ was accompanied by an increase in mRNA level, whereas the ATP-sensitive K+-channel blockers did not change mRNA level. Nifedipine slightly decreased mRNA level. These results suggest that AT2-R expression is sensitively regulated by intracellular cation levels. The change in intracellular Na+ level transcriptionally regulates AT2-R expression, whereas the K+-channel blocker-dependent upregulation appears to be at least in part posttranslational.  (+info)

Ionic currents underlying spontaneous action potentials in isolated cerebellar Purkinje neurons. (2/10550)

Acutely dissociated cell bodies of mouse Purkinje neurons spontaneously fired action potentials at approximately 50 Hz (25 degrees C). To directly measure the ionic currents underlying spontaneous activity, we voltage-clamped the cells using prerecorded spontaneous action potentials (spike trains) as voltage commands and used ionic substitution and selective blockers to isolate individual currents. The largest current flowing during the interspike interval was tetrodotoxin-sensitive sodium current (approximately -50 pA between -65 and -60 mV). Although the neurons had large voltage-dependent calcium currents, the net current blocked by cobalt substitution for calcium was outward at all times during spike trains. Thus, the electrical effect of calcium current is apparently dominated by rapidly activated calcium-dependent potassium currents. Under current clamp, all cells continued firing spontaneously (though approximately 30% more slowly) after block of T-type calcium current by mibefradil, and most cells continued to fire after block of all calcium current by cobalt substitution. Although the neurons possessed hyperpolarization-activated cation current (Ih), little current flowed during spike trains, and block by 1 mM cesium had no effect on firing frequency. The outward potassium currents underlying the repolarization of the spikes were completely blocked by 1 mM TEA. These currents deactivated quickly (<1 msec) after each spike. We conclude that the spontaneous firing of Purkinje neuron cell bodies depends mainly on tetrodotoxin-sensitive sodium current flowing between spikes. The high firing rate is promoted by large potassium currents that repolarize the cell rapidly and deactivate quickly, thus preventing strong hyperpolarization and restoring a high input resistance for subsequent depolarization.  (+info)

Allyl-containing sulfides in garlic increase uncoupling protein content in brown adipose tissue, and noradrenaline and adrenaline secretion in rats. (3/10550)

The effects of garlic supplementation on triglyceride metabolism were investigated by measurements of the degree of thermogenesis in interscapular brown adipose tissue (IBAT), and noradrenaline and adrenaline secretion in rats fed two types of dietary fat. In Experiment 1, rats were given isoenergetic high-fat diets containing either shortening or lard with or without garlic powder supplementation (8 g/kg of diet). After 28 d feeding, body weight, plasma triglyceride levels and the weights of perirenal adipose tissue and epididymal fat pad were significantly lower in rats fed diets supplemented with garlic powder than in those fed diets without garlic powder. The content of mitochondrial protein and uncoupling protein (UCP) in IBAT, and urinary noradrenaline and adrenaline excretion were significantly greater in rats fed a lard diet with garlic powder than in those fed the same diet without garlic. Other than adrenaline secretion, differences due to garlic were significant in rats fed shortening, also. In Experiment 2, the effects of various allyl-containing sulfides present in garlic on noradrenaline and adrenaline secretion were evaluated. Administration of diallyldisulfide, diallyltrisulfide and alliin, organosulfur compounds present in garlic, significantly increased plasma noradrenaline and adrenaline concentrations, whereas the administration of disulfides without allyl residues, diallylmonosulfide and S-allyl-L-cysteine did not increase adrenaline secretion. These results suggest that in rats, allyl-containing sulfides in garlic enhance thermogenesis by increasing UCP content in IBAT, and noradrenaline and adrenaline secretion.  (+info)

UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells. (4/10550)

Uncoupling proteins (UCPs) are a family of mitochondrial transporter proteins that have been implicated in thermoregulatory heat production and maintenance of the basal metabolic rate. We have identified and partially characterized a novel member of the human uncoupling protein family, termed uncoupling protein-4 (UCP4). Protein sequence analyses showed that UCP4 is most related to UCP3 and possesses features characteristic of mitochondrial transporter proteins. Unlike other known UCPs, UCP4 transcripts are exclusively expressed in both fetal and adult brain tissues. UCP4 maps to human chromosome 6p11.2-q12. Consistent with its potential role as an uncoupling protein, UCP4 is localized to the mitochondria and its ectopic expression in mammalian cells reduces mitochondrial membrane potential. These findings suggest that UCP4 may be involved in thermoregulatory heat production and metabolism in the brain.  (+info)

Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion. (5/10550)

Uncoupling protein 2 (UCP2) uncouples respiration from oxidative phosphorylation and may contribute to obesity through effects on energy metabolism. Because basal metabolic rate is decreased in obesity, UCP2 expression is predicted to be reduced. Paradoxically, hepatic expression of UCP2 mRNA is increased in genetically obese (ob/ob) mice. In situ hybridization and immunohistochemical analysis of ob/ob livers demonstrate that UCP2 mRNA and protein expression are increased in hepatocytes, which do not express UCP2 in lean mice. Mitochondria isolated from ob/ob livers exhibit an increased rate of H+ leak which partially dissipates the mitochondrial membrane potential when the rate of electron transport is suppressed. In addition, hepatic ATP stores are reduced and these livers are more vulnerable to necrosis after transient hepatic ischemia. Hence, hepatocytes adapt to obesity by up-regulating UCP2. However, because this decreases the efficiency of energy trapping, the cells become vulnerable to ATP depletion when energy needs increase acutely.  (+info)

A glial-neuronal signaling pathway revealed by mutations in a neurexin-related protein. (6/10550)

In the nervous system, glial cells greatly outnumber neurons but the full extent of their role in determining neural activity remains unknown. Here the axotactin (axo) gene of Drosophila was shown to encode a member of the neurexin protein superfamily secreted by glia and subsequently localized to axonal tracts. Null mutations of axo caused temperature-sensitive paralysis and a corresponding blockade of axonal conduction. Thus, the AXO protein appears to be a component of a glial-neuronal signaling mechanism that helps to determine the membrane electrical properties of target axons.  (+info)

Cloning of a stretch-inhibitable nonselective cation channel. (7/10550)

A homologue of the capsaicin receptor-nonselective cation channel was cloned from the rat kidney to investigate a mechanosensitive channel. We found this channel to be inactivated by membrane stretch and have designated it stretch-inactivated channel (SIC). SIC encodes a 563-amino acid protein with putative six transmembrane segments. The cDNA was expressed in mammalian cells, and electophysiological studies were performed. SIC-induced large cation currents were found to be regulated by cell volume, with currents being stimulated by cell shrinkage and inhibited by cell swelling. Single channel analysis showed a conductance of 250 pS with cation permeability (PCl/PNa < 0.1), and the channel possessed some of the characteristics of a stretch-inactivated channel in that it was permeable to calcium, sensitive to membrane stretch, and blocked by Gd3+. Therefore, we cloned one of the mechanosensitive cation channels of mammals, which is considered to regulate Ca2+ influx in response to mechanical stress on the cell membrane.  (+info)

Modulation of the channel activity of the epsilon2/zeta1-subtype N-methyl D-aspartate receptor by PSD-95. (8/10550)

A channel-associated protein PSD-95 has been shown to induce clustering of N-methyl D-aspartate (NMDA) receptors, interacting with the COOH terminus of the epsilon subunit of the receptors. The effects of PSD-95 on the channel activity of the epsilon2/zeta1 heteromeric NMDA receptor were examined by injection of PSD-95 cRNA into Xenopus oocytes expressing the NMDA receptors. Expression of PSD-95 decreased the sensitivity of the NMDA receptor channels to L-glutamate. Mutational studies showed that the interaction between the COOH terminus of the epsilon2 subunit of the NMDA receptor and the second PSD-95/Dlg/Z0-1 domain of PSD-95 is critical for the decrease in glutamate sensitivity. It is known that protein kinase C markedly potentiates the channel activity of the NMDA receptor expressed in oocytes. PSD-95 inhibited the protein kinase C-mediated potentiation of the channels. Thus, we demonstrated that PSD-95 functionally modulates the channel activity of the epsilon2/zeta1 NMDA receptor. PSD-95 makes signal transmission more efficient by clustering the channels at postsynaptic sites. In addition to this, our results suggest that PSD-95 plays a protective role against neuronal excitotoxicity by decreasing the glutamate sensitivity of the channels and by inhibiting the protein kinase C-mediated potentiation of the channels.  (+info)

Experiments are often performed to study the behaviour of a single ion channel in response to a perturbation produced by a step change (jump) in a variable that influences its equilibrium position, for example a voltage jump or jump in agonist concentration. It is also common to apply a rectangular pulse (consisting of an on jump followed by an off jump); for example brief concentration pulses are used to mimic synaptic transmission.. Assuming a general Markov mechanism for channel dynamics, we obtain theoretical probability distributions of observable characteristics that describe the non-stationary behaviour of single ion channels which are subject to a jump, or to a pulse of finite duration. These characteristics are such things as open times, shut times, first latency, burst length and length of activation. We concentrate particularly on jumps to or from a zero level of agonist, which necessitates some modification to the usual arguments to cope with having some absorbing sets of states. ...
A common concern regarding the use of Xenopus oocytes for the heterologous expression of ion channels is the presence of endogenous channels, which may complicate single-channel studies by providing unwanted background signal (Sobczak et al., 2010; Terhag et al., 2010). An important consideration for our studies was potential interference by endogenous mechanosensitive channels, which have been reported in both excised and cell-attached patches of Xenopus ootyes (Methfessel et al., 1986; Taglietti and Toselli, 1988; Yang and Sachs, 1990; Lane et al., 1991). However, as shown in Fig. 1 B, although endogenous mechanosensitive channels are frequently present in cell-attached patches, they are not active in excised patches under our conditions. Although we cannot completely rule out a minor effect of endogenous channels on our recordings, their contribution to the final conductance measured under tension appears negligible; in traces at relatively high tensions, with all MscS single-channel events ...
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Voltage-gated ion channels play fundamental roles in excitable cells, such as neurons, where they enable electric signaling. Normally, this signaling is well controlled, but brain damage, alterations in the ionic composition of the extracellular solution, or dysfunctional ion channels can increase the electrical excitability thereby causing epilepsy. Voltage-gated ion channels are obvious targets for antiepileptic drugs, and, as a rule of thumb, excitability is dampened either by closing voltagegated sodium channels (Nav channels) or by opening voltage-gated potassium channels (Kv channels). For example, several classical antiepileptic drugs block the ion-conducting pore of Nav channels. Despite the large number of existing antiepileptic drugs, one third of the patients with epilepsy suffer from intractable or pharmacoresistant seizures.. Our research group has earlier described how different polyunsaturated fatty acids (PUFAs) open a Kv channel by binding close to the voltage sensor and, from ...
The cGMP-dependent channel protein has been purified from bovine rod photoreceptor membranes and incorporated into planar lipid membranes. At low divalent cation concentrations, cGMP stimulated single-channel current fluctuations. The probability Po of the channel being open strongly depended on the cGMP concentration (EC50 = 31 microM; Hill coefficient, n = 2.3); whereas the single-channel conductance (lambda = 26 pS) was independent of the agonist concentration. The agonist-stimulated increase in the probability of an open channel was largely due to shorter closed times and, to a lesser extent, due to the channel staying open for a longer time. The current-voltage relationship of the single open channel deviated from ohmic behavior, and the open probability decreased at more negative membrane potentials. The rectification of the macroscopic cGMP-induced current in artificial bilayers that contained many channel copies can be accounted for by the voltage dependence of channel gating together ...
Neuronal ion channels are gated pores whose opening and closing is usually regulated by factors such as voltage or ligands. They are often selectively permeable to ions such as sodium, potassium or calcium. Rapid signalling in neurons requires fast voltage sensitive mechanisms for closing and opening the pore. Anything that interferes with the membrane voltage can alter channel gating and comparatively small changes in the gating properties of a channel can have profound effects. Extremely low frequency electrical or magnetic fields are thought to produce, at most, microvolt changes in neuronal membrane potential. At first sight, such changes in membrane potential seem orders of magnitude too small to significantly influence neuronal signalling. However, in the central nervous system, a number of mechanisms exist which amplify signals. This may allow such small changes in membrane potential to induce significant physiological effects. ...
The voltage sensing domain (VSD) of the voltage-gated proton channel Hv1 mediates a H(+)-selective conductance that is coordinately controlled by the membrane potential (V) and the transmembrane pH gradient (ΔpH). Allosteric control of Hv1 channel opening by ΔpH (V-ΔpH coupling) is manifested by a characteristic shift of approximately 40 mV per ΔpH unit in the activation. To further understand the mechanism for V-ΔpH coupling in Hv1, H(+) current kinetics of activation and deactivation in excised membrane patches were analyzed as a function of the membrane potential and the pH in the intracellular side of the membrane (pHI). In this study, it is shown for the first time to our knowledge that the opening of Hv1 is preceded by a voltage-independent transition. A similar process has been proposed to constitute the step involving coupling between the voltage-sensing and pore domains in tetrameric voltage-gated channels. However, for Hv1, the VSD functions as both the voltage sensor and the conduction
Sigma-Aldrichs Cell Signaling & Neuroscience Voltage-Gated Ion Channels. The majority of ion channels fall into two broad categories: voltage-gated ion channels (VGIC) and ligand-gated ion channels (LGIC). Members of the VGIC superfamily are usually closed at the resting potential of the cell.
Our work focuses on the molecular mechanisms underlying the robustness of neuronal activity. The properties of ion channels or synapses are dynamically regulated to maintain a stable level of activity, despite numerous external or internal disturbances. This stability depends on the dynamic regulation of various ion channels responsible for neuronal activity. We believe that dynamic processes regulate in a coordinated manner the properties of functionally-overlapping ion channels. We seek to determine the mechanisms responsible for the dynamic regulation of ion channels in the dopaminergic neurons of the substantia nigra pars compacta of rodents. These neurons are able to spontaneously generate regular activity patterns in the absence of any stimuli (including synaptic inputs). This "pacemaker" property allows us to precisely define their patterns of activity in vitro and to determine the causal relationships between the properties of the voltage-gated ion channels expressed by these neurons and ...
Only a few years ago, in 2011, the Sternson group exploited the properties of specialized domains to engineer new ligand-gated channels, which they called PSAMs2. First, the Sternson group made the critical observation that ligand-gated (i.e. molecule-sensing) ion channels can be divided into two somewhat independent domains, the ligand-binding domain and the ion channel domain. By screening candidate mutations in the ligand-binding domain of a starter channel, they were able to engineer the channel to lose its innate affinity to its natural ligand and acquire a preference for a synthetic molecule. By transplanting this new ligand binding domain onto other excitatory and inhibitory ion channel domains, the Sternson group successfully created novel excitatory and inhibitory channels. These channels now specialize in binding synthetic ligands that have never occurred in any biological system and are used as a tool to manipulate neuron activities.. Recent work by researchers in the Jan labs ...
A transformed line of human embryonic kidney epithelial cells (HEK 293) is commonly used as an expression system for exogenous ion channel genes. Previously, it has been shown that these cells contain mRNAs for a variety of ion channels. Expression of some of these genes has been confirmed at the protein level. Patch-clamp electrophysiology experiments confirm the presence of multiple ion channels and molecular data agree with pharmacological profiles of identified channels. In this work, we show that endogenous voltage-gated potassium channels in HEK cells are a significant source of outward current at positive potentials. We show that both non-transfected HEK cells and HEK cells transfected with hyperpolarization-activated cyclic-nucleotide gated (HCN) channels have a significant amount of voltage-gated potassium (K(V)) current when certain tail current voltage-clamp protocols are used to assay HCN current activation. Specifically, tail current protocols that use a depolarized holding ...
Ion channels are transmembrane proteins that allow ions to move in or out of cells, and they are vital to a range of biological processes. They can be opened and closed in a number of ways: for example, some are opened by voltage, while others respond to the binding of ligands. Piezo1 and Piezo2 are mechanosensitive ion channels: in other words, they open in response to mechanical stimulation, such as stretching or shear stress (Coste et al., 2010, 2012).. Mutations in the gene Piezo1 have been linked to a blood disease called xerocytosis that leads to hemolytic anemia (Albuisson et al., 2013; Bae et al., 2013; Coste et al., 2013; Zarychanski et al., 2013). It is known that these mutations reduce the ability of the Piezo1 ion channel to close, and this leads to red blood cells shrinking as a result of dehydration. However, the details of this process are not fully understood. Now, in a pair of papers in eLife, Ardem Patapoutian, Michael Bandell and colleagues at the Scripps Research Institute, ...
Ion channel conformational changes within the lipid membrane are a key requirement to control ion passage. Thus, it seems reasonable to assume that lipid composition should modulate ion channel function. There is increasing evidence that this implicates not just an indirect consequence of the lipid influence on the physical properties of the membrane, but also specific binding of selected lipids to certain protein domains. The result is that channel function and its consequences on excitability, contractility, intracellular signaling or any other process mediated by such channel proteins, could be subjected to modulation by membrane lipids. From this it follows that development, age, diet or diseases that alter lipid composition should also have an influence on those cellular properties. The wealth of data on the non-annular lipid binding sites in potassium channel from Streptomyces lividans (KcsA) makes this protein a good model to study the modulation of ion channel structure and function by lipids.
Concentration-dependent biphasic effects of drugs on ion channel activity have been reported in a variety of preparations, usually with stimulatory effects seen at low concentrations followed by increasingly dominant inhibition at higher levels. Such behaviour is often interpreted as evidence for the existence of separate modulatory drug binding sites. We demonstrate in this paper that it is possible for biphasic effects to be produced in an allosteric model of a ligand-activated ion channel, where diffusion-limited binding of the modulatory drug is restricted to either a stimulatory or an inhibitory site (but not both) because of steric overlap. The possibility of such an interaction mechanism should be kept in mind when interpreting experimental data if stoichiometric evidence from complementary techniques suggests that only one drug molecule is bound per receptor/ion channel complex.. ...
Dopaminergic neurons of the substantia nigra pars compacta (SNc) are involved in the control of movement, sleep, reward, learning, and nervous system disorders and disease. To date, a thorough characterization of the ion channel phenotype of this important neuronal population is lacking. Using immunohistochemistry, we analyzed the somatodendritic expression of voltage-gated ion channel subunits that are involved in pacemaking activity in SNc dopaminergic neurons in 6-, 21-, and 40-day-old rats. Our results demonstrate that the same complement of somatodendritic ion channels is present in SNc dopaminergic neurons from P6 to P40. The major developmental changes were an increase in the dendritic range of the immunolabeling for the HCN, T-type calcium, Kv4.3, delayed rectifier, and SK channels. Our study sheds light on the ion channel subunits that contribute to the somatodendritic delayed rectifier (Kv1.3, Kv2.1, Kv3.2, Kv3.3), A-type (Kv4.3) and calcium-activated SK (SK1, SK2, SK3) potassium ...
To investigate the cellular mechanism responsible for the apical membrane Cl conductance in airway epithelia, we used the patch-clamp technique to study single ion channels in primary cultures of...
Spontaneously opening, chloride-selective channels that showed outward rectification were recorded in ripped-off patches from rat cultured hippocampal neurons and in cell-attached patches from rat hippocampal CA1 pyramidal neurons in slices. In both preparations, channels had multiple conductance states and the most common single-channel conductance varied. In the outside-out patches it ranged from 12 to 70 pS (Vp=40 mV) whereas in the cell-attached patches it ranged from 56 to 85 pS (-Vp=80 mV). Application of GABA to a patch showing spontaneous channel activity evoked a rapid, synchronous activation of channels. During prolonged exposure to either 5 or 100 microM GABA, the open probability of channels decreased. Application of GABA appeared to have no immediate effect on single-channel conductance. Exposure of the patches to 100 microM bicuculline caused a gradual decrease on the single-channel conductance of the spontaneous channels. The time for complete inhibition to take place was slower ...
An input/output data channel operates in conjunction with a virtual memory computer. A channel operation is commenced with the execution of a start I/O instruction which transfers a channel address word (CAW) to the channel. The CAW contains a virtual command address pointing to the beginning of a virtual channel program. The virtual command address is presented to a channel look-aside buffer which translates the virtual command to a real memory address for accessing main storage. The virtual channel command words (CCWs) which comprise the channel program are successively translated by the channel look-aside buffer. A virtual address stack within the buffer holds active virtual data addresses and command addresses for each channel. Interlocking between this stack and a CPU translation mechanism is provided by an I/O bit array. The I/O bit array contains a count mechanism for each memory frame which may be addressed by the channel. Each time a memory frame is addressed by any of the channels, the
Neurons are highly polarized cells with apparent functional and morphological differences between dendrites and axon. A critical determinant for the molecular and functional identity of axonal and dendritic segments is the restricted expression of voltage-gated ion channels. Several studies show an uneven distribution of ion channels and their differential regulation within dendrites and axons, which is a prerequisite for an appropriate integration of synaptic inputs and the generation of adequate action potential firing patterns. This review will focus on the signaling pathways leading to segmented expression of voltage-gated potassium and sodium ion channels at the neuronal plasma membrane and the regulatory mechanisms ensuring segregated functions. We will also discuss the relevance of proper ion channel targeting for neuronal physiology and how alterations in polarized distribution contribute to neuronal pathology.
Trimeric intracellular cation-selective (TRIC) channel subtypes, namely TRIC-A and TRIC-B, are derived from distinct genes and distributed throughout the sarco/endoplasmic reticulum (SR/ER) and nuclear membranes. TRIC-A is preferentially expressed at high levels in excitable tissues, while TRIC-B is ubiquitously detected at relatively low levels in various tissues. TRIC channels are composed of ~300 amino acid residues and contain three putative membrane-spanning segments to form a bullet-shaped homo-trimeric assembly. Both native and purified recombinant TRIC subtypes form functional monovalent cation-selective channels in a lipid bilayer reconstitution system. The electrophysiological data indicate that TRIC channels behave as K(+) channels under intracellular conditions, although the detailed channel characteristics remain to be investigated. The pathophysiological defects detected in knockout mice suggest that TRIC channels support SR/ER Ca(2+) release mediated by ryanodine (RyR) and inositol
The invention relates to the field of drug delivery, in particular, to compounds and methods for the chemical modification of a proteinaceous channel to be used in pharmaceutical delivery vehicles for controlled and/or localized release of therapeutic molecules (e.g., small molecules, peptides, proteins or other macromolecules). Provided are pH- and/or light-responsive compounds capable of controlling the channel activity of a mechanosensitive channel, such as the MscL channel protein of E. coli, or a functional equivalent thereof, and use of these compounds to convert a mechanosensitive channel protein into a pH- and/or light-responsive channel. Also provided are drug delivery vehicles comprising a pH- and/or light-responsive channel protein.
Typically the activities of the ion channels are not called firing patterns as in neuroscience we refer to "firing" when we mean the elicitation of action potentials (spikes) but yes: Whenever an AP was fired a sufficient amount of sodium channels had to be open and therefore I thing your reasoning is correct. In other terms what you are saying is that the effective channel conductances change during an action potential.. On your conclusion: In the regime of natural parameters the time scale of firing pattern 1 mostly depends on the time constants of the voltage gated ion channels and not so much on the absolute number of channels (especially if all the conductances would scale equally). In the world of Hodgin-Huxley like coupled- and nonlinear-dynamical systems the voltage does not scale strictly linear with increasing the participating max. conductances. The interplay of max. conductance and temporal gating dynamics resulting in the effective conductance itself depends on the voltage and there ...
Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits. [provided by RefSeq, Oct 2012 ...
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This study reports the formation of self-assembled transmembrane anion channels by small-molecule fumaramides. Such artificial ion channel formation was confirmed by ion transport across liposomes and by planar bilayer conductance measurements. The geometry-optimized model of the channel and Cl− ion selectivity wit
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:12527813, PubMed:21233214). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:20696761). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772, PubMed:8495559, PubMed:11211111, PubMed:23769686). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:8495559, PubMed:20220134). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location ...
Glutamate activates a number of different receptor-channel complexes, each of which may contribute to generation of excitatory postsynaptic potentials in the mammalian central nervous system. The rapid application of the selective glutamate agonist, quisqualate, activates a large rapidly inactivating current (3 to 8 milliseconds), which is mediated by a neuronal ionic channel with high unitary conductance (35 picosiemens). The current through this channel shows pharmacologic characteristics similar to those observed for the fast excitatory postsynaptic current (EPSC); it reverses near 0 millivolts and shows no significant voltage dependence. The amplitude of the current through this channel is many times larger than that through the other non-NMDA (N-methyl-D-aspartate) channels. These results suggest that this high-conductance quisqualate-activated channel may mediate the fast EPSC in the mammalian central nervous system. ...
Changes of the electrical charges across the surface cell membrane are absolutely necessary to maintain cellular homeostasis in physiological as well as in pathological conditions. The opening of ion channels alter the charge distribution across the surface membrane as they allow the diffusion of ions such as K+, Ca++, Cl−, Na+. Traditionally, voltage-gated ion channels (VGIC) are known to play fundamental roles in controlling rapid bioelectrical signaling including action potential and/or contraction. However, several investigations have revealed that these classes of proteins can also contribute significantly to cell mitotic biochemical signaling, cell cycle progression, as well as cell volume regulation. All these functions are critically important for cancer cell proliferation. Interestingly, a variety of distinct VGICs are expressed in different cancer cell types, including metastasis but not in the tissues from which these tumors were generated. Given the increasing evidence suggesting ...
Plant growth depends on the maintenance of the adequate intracellular levels of potassium ion (K+). Different abiotic stresses threaten this homeostasis, thus, the characterization of the molecules involved in the regulation of cytoplasmic K+ concentration is important as they could be targeted for plant crop improvement. The families of 10 Calcineurin B like (CBL) calcium sensors and 26 CBL-Interacting Protein Kinases (CIPK) decode the calcium signals elicited by stress and regulate different ion channels and transporters involved in the control of K+ fluxes in plants. Nevertheless, the detailed molecular mechanisms balancing specificity and versatility to the system require investigation. Here, we show that the cytosolic domain of t he inwardrectifier K+ channel (AKT1) harbors a non-canonical ankyrin domain which is not essential for channel function but serves as a docking site for its regulator, the CIPK23 protein kinase. Mutations on this domain impair kinase channel association. This ...
The PMX multi channel data acquisition system can be used to measure and control in real-time. This system is ideal for production and quality assurance.
TY - JOUR. T1 - Inhibition of ligand-gated cation-selective channels by tamoxifen. AU - Allen, Marcus. AU - Newland, Claire. AU - Valverde, Miguel A.. AU - Hardy, Simon. PY - 1998/9/16. Y1 - 1998/9/16. U2 - 10.1016/S0014-2999(98)00454-3. DO - 10.1016/S0014-2999(98)00454-3. M3 - Article. VL - 354. SP - 261. EP - 269. JO - European Journal of Pharmacology. JF - European Journal of Pharmacology. SN - 0014-2999. IS - 2-3. ER - ...
Ligand-gated ion channels (LGICs) are a group of transmembrane ion channel proteins which open to allow ions such as Na+, K+, Ca2+, or Cl- t ...
K+ selective channels are some of the most widespread ion trafficking molecules in living organisms, with more than 70 genes encoding different K+ channels in humans. KV channels fall into one of the two classical categories of delayed rectifier (DR) and A-type. Delayed rectifier was the original name attributed to voltage-dependent K+ channels due to their delayed activation in squid giant axons. A-type channels are low voltage-activated, fast inactivating (therefore, transient) K+ channels. Specific KV toxins are often used to dissect the particular contribution of different subunits to native currents.. Alomone Labs is excited to offer a line of Overexpressed Membrane Fractions. These membrane fractions are Xenopus oocyte membrane lysates overexpressing a specific ion channel. Fractions are sold as a set of injected and non-injected oocytes and can be used as controls for Alomone Labs antibodies. Overexpressed Membrane Fractions can also be purchased as a kit with their respective antibody. ...
What is difference between Ion Channel and Transporter? Ion channel involves in passive transportation of ions while, transporter involves active transportation
TY - JOUR. T1 - Kv2.1 channels play opposing roles in regulating membrane potential, Ca2+ channel function, and myogenic tone in arterial smooth muscle. AU - ODwyer, Samantha C.. AU - Palacio, Stephanie. AU - Matsumoto, Collin. AU - Guarina, Laura. AU - Klug, Nicholas R.. AU - Tajada, Sendoa. AU - Rosati, Barbara. AU - McKinnon, David. AU - Trimmer, James S.. AU - Santana, L. Fernando. PY - 2020/2/18. Y1 - 2020/2/18. N2 - The accepted role of the protein Kv2.1 in arterial smooth muscle cells is to form K+ channels in the sarcolemma. Opening of Kv2.1 channels causes membrane hyperpolarization, which decreases the activity of L-type CaV1.2 channels, lowering intracellular Ca2+ ([Ca2+]i) and causing smooth muscle relaxation. A limitation of this model is that it is based exclusively on data from male arterial myocytes. Here, we used a combination of electrophysiology as well as imaging approaches to investigate the role of Kv2.1 channels in male and female arterial myocytes. We confirmed that ...
As ion channels influence many aspects of biology, artificially light-responsive ion channels can facilitate experimental manipulation, allowing neuro
The ability of an organism to detect injury or potentially harmful thermal, mechanical and chemical stimuli - a process generally referred to as nociception - is crucial for survival. The recent discovery of TRP channels as molecular sensors of multiple noxious stimulus modalities (thermal, mechanical and chemical stimuli) in primary sensory neurons has opened-up new avenues for understanding how organisms monitor their internal and external environment. The first TRP ion channel was identified in a Drosophila melanogaster (a fruit fly) mutant, in which the photoreceptor cells responded with a transient rather than a sustained receptor potential to continuous light. The mutant was therefore named trp. The trp gene encodes a calcium permeable ion channel - the founding member of a large family of cation channels present in worms, insects, fish and mammals. However, the discovery of mammalian thermosensitive TRP ion channels in sensory neurons was triggered by the use of natural products derived from
Ion channels are integral membrane proteins that provide controlled pathways for ion passage through cellular membranes. Cation selective channels play important roles in physiological processes such as secretory transduction, control of ion homeostasis, cell volume, vesicle cycling, and electrical control of excitable tissues. The importance of cation channels is also amplified by the fact that many therapeutic drugs mediate their effects by targeting these proteins. Potassium-selective channels are the most genetically diverse of all cation channels. Starting with the first cloned potassium selective ion channel from Drosophila melanogaster, Shaker, more than 100 potassium channels have been identified. The number of functionally distinct channels in native tissues is further increased by heteromultimeric assembly of potassium channel α-subunits with other α- and β-subunits and other modifications such as alternative splicing of mRNAs, glycosylation, and phosphorylation. In light of the ...
Bicuculline methiodide (BIC-Mel) (10-100 microM) altered the kinetics of N-methyl-D-aspartate (NMDA) responses in single-channel and whole-cell recordings. The principal effect of BIC-Mel (10-100 microM) on NMDA channels was a dose-dependent decrease in mean channel open time (tau o), accompanied by the introduction of a new closed time (tau B) of 14.0 +/- 3.5 msec (mean +/- standard deviation; n = 14) in closed time distributions, which was independent of BIC-Mel concentration. BIC-Mel (10-100 microM) increased the frequency of NMDA channel opening in a dose-dependent manner, offsetting the decrease in tau o, such that the total time spent in the open state per minute was unchanged, and thus the total charge/min through NMDA channels was unchanged. Similarly, the amplitudes of NMDA whole-cell current responses were not noticeably affected by 10-80 microM BIC-Mel, even though power spectra density analysis of the whole-cell NMDA-stimulated noise revealed changes in the underlying channel ...
Mechanosensitive ion channels (MS channels) represent a diverse population of ion channels. Other membrane-associated proteins with different biophysical properties apart from ion channels, specialized cytoskeletal proteins, cell junction molecules and G-protein-coupled receptors and kinases, among many others are also considered mechanosensitive. MS channels integrate a variety of mechanical stimuli such as shear stress, tension, torsion, and compression and translate them into short-term effects (i.e., changes in ion concentrations and voltage) and long-term effects via changes in gene expression. ...
The experimental results summarized in Fig. 4 can be explained by assuming that the open probability of rod and olf CNG channels is governed by the balance of the action of three relatively independent regions: the NH2 terminus, the NBD, and the core-CL region. Corresponding regions in rod and olf show characteristically different actions. These actions may be summarized as follows. First, the NBD exerts the leading effect on channel opening. This effect is strongly promoted by increasing the [cGMP]. The NBD of rod has a slightly larger opening effect than the NBD of olf at all [cGMP]. Second, the core-CL region has a much weaker and cGMP-independent effect on the channel opening compared with the NBD. The core-CL region of olf favors opening more than the core-CL region of rod. Finally, the NH2 termini have differential effects on channel opening: the olf NH2 terminus promotes channel opening with both olf and rod core-CL region. In contrast, the rod NH2 terminus promotes opening only with the ...
Business Overview from 10-K filing for Icagen, Inc.:. We are a biopharmaceutical company focused on the discovery, development and commercialization of novel orally-administered small molecule drugs that modulate ion channel targets. Ions are charged particles, such as sodium, potassium, calcium and chloride. Ion channels are protein structures found in virtually every cell of the human body. Ion channels span the cell membrane and regulate the flow of ions into and out of cells. There are currently over 35 drugs marketed by third parties for multiple indications that modulate ion channels according to data from IMS Health. We believe this demonstrates that ion channels are attractive drug targets. Utilizing our proprietary know-how and integrated scientific and drug development capabilities, we have identified multiple drug candidates that modulate ion channels. ...
A number of potassium channels including members of the KCNQ family and the Ca2+ activated IK and SK, but not BK, are strongly and reversibly regulated by small changes in cell volume. It has been argued that this general regulation is mediated through sensitivity to changes in membrane stretch. To test this hypothesis we have studied the regulation of KCNQ1 and BK channels after expression in Xenopus oocytes. Results from cell-attached patch clamp studies (∼50 μm2 macropatches) in oocytes expressing BK channels demonstrate that the macroscopic volume-insensitive BK current increases with increasing negative hydrostatic pressure (suction) applied to the pipette. Thus, at a pipette pressure of−5.0±0.1 mmHgthe increase amounted to 381±146% (mean±s.e.m., n =6, P ,0.025). In contrast, in oocytes expressing the strongly volume-sensitive KCNQ1 channel, the current was not affected by membrane stretch. The results indicate that (1) activation of BK channels by local membrane stretch is not ...
Ion Channels in the Cardiovascular System in Health and Disease. William A. Coetzee [email protected] Tel: 263-8518. Hearts are Composed of Cells. The Cardiac Myocyte. Cells Have Membranes. Channels. Pore. Filter. Gate. Patch Clamping. open. closed. Ion Channels - Gating. Slideshow 85327...
Rival design plans for two mooted TV entertainment channels are emerging from Channel 4 and the BBC.. Channel 4 is still awaiting the final go-ahead for its digital entertainment channel E4 before awarding a branding contract. Meanwhile, the BBC, reported to be rebranding and repositioning BBC Choice as BBC3, officially denies it has plans to do so.. E4 head of marketing Dan Brooke expects there to be a pitch to choose design and branding consultancies as soon as the financial go ahead for the project is agreed in the next few months.. Brooke says: "I think we can expect all of those things to happen when we get the go ahead. At the moment the channel is going through the final stages of the green light process.". Channel 4 incumbent consultancy Static 2358 has already worked on the initial conception and presentation for E4. Brooke expects to have determined a plan of action by next month.. The altogether less certain BBC 3 is reported to be launching as an entertainment channel this summer, ...
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Channel numbers refer to the physical channels transmitted in the OggPCM stream. They start at zero, denoting the first channel transmitted in a frame, and range to the number of channels indicated in the main header packet minus one. References to absent channels MUST be treated as an error. If a physical channel is not referenced in any of the channel maps and defaulting is not being used, its semantics are unknown. Such channels SHOULD NOT be played without user intervention, and SHOULD NOT be routed to audio outputs which are currently in use, but they MUST NOT be considered an error. Channel_types refer to logical channels with a clear interpretation on how the sound data routed to them is to be reproduced. All channel_types less than 0x80000000 are reserved for use by Xiph; 0x80000000 and above are allowed for application specific extensions. This scheme allows for 2^31 -1 Xiph defined channel map types and 2^32 distinct channel names. If a channel_type which has not been defined is ...
Channel numbers refer to the physical channels transmitted in the OggPCM stream. They start at zero, denoting the first channel transmitted in a frame, and range to the number of channels indicated in the main header packet minus one. References to absent channels MUST be treated as an error. If a physical channel is not referenced in any of the channel maps and defaulting is not being used, its semantics are unknown. Such channels SHOULD NOT be played without user intervention, and SHOULD NOT be routed to audio outputs which are currently in use, but they MUST NOT be considered an error. Channel_types refer to logical channels with a clear interpretation on how the sound data routed to them is to be reproduced. All channel_types less than 0x80000000 are reserved for use by Xiph; 0x80000000 and above are allowed for application specific extensions. This scheme allows for 2^31 -1 Xiph defined channel map types and 2^32 distinct channel names. If a channel_type which has not been defined is ...
All the data gathered on the effects of PIP2 on Kir6.2/SUR1 channels can be interpreted by a stabilization of the channel in the open conformation (Enkvetchakul et al., 2000). Similarly, our data can also be interpreted by a model based on the stabilization by PIP2 of the open conformation of KCNQ1/KCNE1 channels. This model is also comparable to Shaker channels kinetic models, i.e. one or more transitions of the four subunits followed by one or more additional concerted transitions (Schoppa and Sigworth, 1998). In the model that we used, one transition of the four subunits and one concerted transition were sufficient to convincingly fit the data. The model illustrates how variations in PIP2 levels are accompanied by changes in deactivation with no changes in activation kinetics. The requirement of the four domains to be in the on state to allow the channel to finally open makes this transition slow and rate limiting. Since this step is PIP2‐independent (kS4 is constant and k′S4 ...
Ion channel function[edit]. Each AMPAR has four sites to which an agonist (such as glutamate) can bind, one for each subunit.[5 ... Mayer, M. L. (2005). "Glutamate receptor ion channels". Current Opinion in Neurobiology. 15 (3): 282-288. doi:10.1016/j.conb. ... The AMPA receptor GluA2 (GluR2) tetramer was the first glutamate receptor ion channel to be crystallized. ... preventing the flux of potassium ions through the channel pore. GluA2-lacking AMPARs are, thus, said to have an inwardly ...
Alpha-helical channels including ion channels[edit]. *Voltage-gated ion channel like, including potassium channels KcsA and ... They are ligand-gated outer membrane channels (n=22,S=24), including cobalamin transporter BtuB, Fe(III)-pyochelin receptor ... The translocon channel provides a highly heterogeneous environment for the nascent transmembane α-helices. A relatively polar ... Chloride channels. *Outer membrane auxiliary proteins (polysaccharide transporter) - α-helical transmembrane proteins from the ...
Ion channels: Ion channel modulators. *TRP channel modulators. *Transporters: Sodium-glucose transporter modulators ...
Diseases of ion channels. Calcium channel. Voltage-gated. *CACNA1A *Familial hemiplegic migraine 1 ...
The condition has been linked with genetic mutations in genes that code for certain ion channels that transport electrolytes ( ... The concept of channelopathies and the link with specific ion channel mutations emerged at the end of the 20th century.[1][3][4 ... implying that transcription of the gene and production of ion channels may be altered by increased thyroid hormone levels. ... which have been linked with mutations in ion channels; the majority of these conditions occurs episodically.[3] ...
Diseases of ion channels. Calcium channel. Voltage-gated. *CACNA1A *Familial hemiplegic migraine 1 ...
Some genes encode ion channels that carry calcium or potassium ions (CACNA1C, CACNB2, KCND3, KCNE3, KCNJ8),[15] while others ... The first mutations described in association with Brugada syndrome were in a gene responsible for a protein or ion channel that ... Some are responsible for other proteins that form part of the sodium channel, known as sodium channel β subunits (SCN1B, SCN2B ... "Ion Channel Disorders and Sudden Cardiac Death". International Journal of Molecular Sciences. 19 (3): 692. doi:10.3390/ ...
Kaupp UB, Seifert R (July 2002). "Cyclic nucleotide-gated ion channels". Physiol. Rev. 82 (3): 769-824. CiteSeerX 10.1.1.319. ... "A β2 adrenergic receptor signaling complex assembled with the Ca2+ channel Cav1.2". Science. 293 (5527): 98-101. doi:10.1126/ ...
Darszon, A., labarca, P., Nishigaki, T., and Espinosa, F. (1999). Ion channels in sperm physiology. Physiol. Rev 79, 481-510 ... Sperm movement is activated by changes in intracellular ion concentration.[2] The changes in ion concentration that provoke ... In some mammals, sperm motility is activated by increase in pH, calcium ion and cAMP, yet it is suppressed by low pH in the ... As a result, sperm movement is activated.[3] The change in cell volume which alters intracellular ion concentration can also ...
... and ion channels.. Receptor proteins can be classified by their location. Transmembrane receptors include ion channel-linked ( ... cyclic nucleotide-gated ion channels. cGMP (vision), cAMP and cGTP (olfaction). Na+, K+ [11]. ... This is seen with ion channel receptors.. *Uncoupling of the receptor effector molecules is seen with G-protein couple receptor ... activation of these receptors results in changes in ion movement across a membrane. They have a heteromeric structure in that ...
Ion channel. *Calcium channel blocker (CCB). *Potassium channel blocker (PCB). *Sodium channel blocker (SCB) ... John's wort specifically activates TRPC6 channels". The FASEB Journal. 21 (14): 4101-11. doi:10.1096/fj.07-8110com. PMID ... and they exert these effects by binding to and activating the transient receptor potential cation channel TRPC6.[24][27] ... "The involvement of sodium and calcium ions in the release of amino acid neurotransmitters from mouse cortical slices elicited ...
Major receptor types studied in pharmacology include G protein coupled receptors, ligand gated ion channels and receptor ...
Ion channel. See Ion channel modulators. Receptor &. transporter. BA/M. Adrenergic. *Adrenergic receptor agonist (α ...
... however some neuropeptides directly gate ion channels or act through kinase receptors. ...
"Ion Channels of the Mammalian Urethra". Channels. 8 (5): 393-401. doi:10.4161/19336950.2014.954224. PMC 4594508. PMID 25483582. ...
Ion channel. modulators. Calcium blockers. *Gabapentin. *Gabapentin enacarbil. *Mirogabalin. *Pregabalin. *Ziconotide. Sodium ...
Ion channel blockers. *Anticonvulsants (e.g., gabapentin, pregabalin, carbamazepine, oxcarbazepine, lacosamide, lamotrigine) ... but could relate to actions of the drug on voltage-activated calcium channels. Lamotrigine blocks T-type calcium channels ... Lamotrigine is a member of the sodium channel blocking class of antiepileptic drugs.[60] This may suppress the release of ... It also blocks L-, N-, and P-type calcium channels and has weak 5-hydroxytryptamine-3 (5-HT3) receptor inhibition. These ...
5-HT3 serotonin ion. channel antagonists. *Alosetron. *Azasetron. *Bemesetron. *Cilansetron. *Clozapine ... The cause is thought to be blockade of hERG voltage-gated potassium channels.[41][42] The risks are dose-dependent, and appear ... the voltage-gated potassium channel KCNH2 gene (hERG/Kv11.1), and the α1D-adrenoceptor ADRA1D gene.[58] ...
They are particularly well known in pharmacology as L-type calcium channel blockers, used in the treatment of hypertension. ... Compared with certain other L-type calcium channel blockers (for example those of the phenylalkylamine class such as verapamil ... The pharmaceutical drug finerenone is also a dihydrophyridine derivative, but does not act as a calcium channel blocker but as ... Dihydropyridine class L-type calcium channel blockers include, in alphabetical order (brand names vary in different countries ...
Ion channel. modulators. Calcium blockers. *Gabapentin. *Gabapentin enacarbil. *Pregabalin. *Ziconotide. Sodium blockers. * ...
Ion channel blockers. *Anticonvulsants (e.g., gabapentin, pregabalin, carbamazepine, oxcarbazepine, lacosamide, lamotrigine) ... and sodium channels in the cardiac muscle, leading to decreased cardiac conduction and cardiotoxicity. Selectivity of ...
Binds to the α2δ-1 subunit of voltage gated calcium ion channels in the spinal cord. May also modulate NMDA receptors and ... N-type calcium-channel blocker.. Intrathecal.. Protein binding = 50%; half-life = 2.9-6.5 hours; excretion = urine (,1%).[122] ... Flupirtine is a centrally acting K+ channel opener with weak NMDA antagonist properties.[34] It is used in Europe for moderate ... Potassium channel (Kv7) opener.[116]. PO, rectal.. Bioavailability = 90% (oral), 72.5% (rectal); protein binding = 80%; volume ...
Ion channel modulators. Calcium. VDCCs. Blockers. *L-type-selective: Dihydropyridines: Amlodipine. *Aranidipine ...
Ion channel blockers. *Anticonvulsants (e.g., gabapentin, pregabalin, mirogabalin, carbamazepine, oxcarbazepine, lacosamide, ... Carbamazepine is a sodium channel blocker.[28] It binds preferentially to voltage-gated sodium channels in their inactive ... and calcium channel blockers.[12] Carbamazepine also increases the metabolism of the hormones in birth control pills and can ...
α2δ subunit-containing voltage-dependent calcium channels blockers (gabapentinoids) (e.g., gabapentin, pregabalin, phenibut) ... δ subunit-containing voltage-dependent calcium channels (VDCCs), similarly to gabapentinoids like gabapentin and pregabalin.[9] ... δ subunit-containing voltage-gated calcium channel blocker or gabapentinoid may be its true primary mechanism of action, and ... "R-phenibut binds to the α2-δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects ...
Voltage sensitive ion channels are glycoprotein molecules which extend through the lipid bilayer, allowing ions to traverse ...
We examine this issue by way of the model protein Gloeobacter violaceous ligand-gated ion channel (GLIC) using computational ... General anesthetics bind reversibly to ion channels, modifying their global conformational distributions, but the underlying ...
Blaustein RO, Finkelstein A. Diffusion limitation in the block by symmetric tetraalkylammonium ions of anthrax toxin channels ... T1 - Diffusion limitation in the block by symmetric tetraalkylammonium ions of anthrax toxin channels in planar phospholipid ... Diffusion limitation in the block by symmetric tetraalkylammonium ions of anthrax toxin channels in planar phospholipid bilayer ... Diffusion limitation in the block by symmetric tetraalkylammonium ions of anthrax toxin channels in planar phospholipid bilayer ...
Biophysical and ion channel functional characterization of the Torpedo californica nicotinic acetylcholine receptor in varying ... and planar lipid bilayers to measure ion channel function. Detergent solubilization of nAChR-enriched membranes did not result ... maintaining stability and supporting ion channel function, while non-lipid analog detergents [Cymal-6 (6-Cyclohexyl-1-hexyl-β-d ... maintaining moderate stability and ion channel function when compared to lipid-analog detergents. Overall, these results show ...
The Acid-sensing Ion Channel (ASIC) detects changes in pH levels in the organism and transmits the pain signal to the brain. ... al., Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking of ASIC2b via Heteromeric Assembly, Scientific Reports ... Biologically, many studies have been conducted regarding the Acid-sensing Ion Channel; however, many areas are still unclear, ... That our study investigated a new control mechanism of the Acid-sensing Ion Channel has important implications. Through ...
Dibas, A, Millar, JC, Al-Farra, A & Yorio, T 2018, Neuroprotective Effects of Psalmotoxin-1, an Acid-Sensing Ion Channel (ASIC ... N2 - Purpose: The purpose of the current study is to assess changes in the expression of Acid-Sensing Ion Channel (ASIC)1a and ... AB - Purpose: The purpose of the current study is to assess changes in the expression of Acid-Sensing Ion Channel (ASIC)1a and ... Purpose: The purpose of the current study is to assess changes in the expression of Acid-Sensing Ion Channel (ASIC)1a and ASIC2 ...
The action of adamantanamines against influenza A viruses: inhibition of the M2 ion channel protein. Semin Virol. 1992; 3:21-30 ...
... ions across the cell membrane are responsible for the rhythmic beating of heart cells. ... Channels that control the flow of potassium (K+) and sodium (Na+) ... called ion channels. Some valves let certain ions like potassium (K+) flow out, others let different ions like sodium (Na+) ... When a heart cell beats, sodium channels open allowing a rapid, transient in-rush of Na+ ions, then close within about two one- ...
Ion Channels and Ion Pumps. Metabolic and Endocrine Relationships in Biology and Clinical Medicine. ... Characterization of Ion Channels in the Central Nervous System: Insights from Radioligand Binding, Autoradiography, and In Situ ... Calcium Ion Homeostasis in the Aging Brain: Regulation of Voltage-Dependent Calcium Channels ... Interactions of Ethanol with Ion Channels: Possible Implications for Mechanisms of Intoxication and Dependence ...
Ion Flux Dependent and Independent Functions of Ion Channels in the Vertebrate Heart: Lessons Learned from Zebrafish, Mirjam ... Stem Cells and Ion Channels. Guest Editors: Stefan Liebau, Alexander Kleger, Michael Levin, and Shan Ping Yu *Stem Cells and ... Ion Channel Activities in Neural Stem Cells of the Neuroepithelium, Masayuki Yamashita Review Article (6 pages), Article ID ... Ion Channels in Hematopoietic and Mesenchymal Stem Cells, Serena Pillozzi and Andrea Becchetti Review Article (9 pages), ...
Experimental investigation of ligand-gated ion channels, with Forschungszentrum Jülich - FZJ - Helmholtz Association. Apply ... PhD Position: Experimental investigation of ligand-gated ion channels. Forschungszentrum Jülich - FZJ - Helmholtz Association. ... The Department of Molecular Pharmacology offers state-of-the-art methods to study ligand-gated ion channels by ... we are looking for a PhD student to join our research group on ion channels and transporters. In the frame of a research ...
... campaigns on an expanding list of channel types. Chronologically, HTS methods for ion channels include the ligand binding assay ... Therefore, ion channels represent a class of attractive drug targets and a class of important off-targets for in vitro ... In this review we summarize the current HTS technologies for different ion channel classes and their applications. ... Ion channels are involved in a variety of fundamental physiological processes, and their malfunction causes numerous human ...
The study of ion channels is called electrophysiology, and is described in this article. ... Ion channels are imperative to the normal functioning of the cell. ... Ion channels are proteins embedded in the cell membrane which control the bidirectional movement of charged species called ions ... Ion channels are highly selective and can be grouped according to their structure, either as members of the voltage-gated or ...
... chrissy chrissy_4u2c at hotmail.com Thu Oct 30 07:30:23 EST 2003 *Previous message: UV laser for DNA ... With a multisubunit ion channel, where the subunits have multiple transmembrane helices, how do you tell which of a subunits ... And how does that relate to ligand-gated channels in general? *Previous message: UV laser for DNA-protein cross-linking ...
Such channels control the transmembrane flow of ions by opening or closing in response to appropriate... ... Ion channels are protein pores that provide for the rapid movement of ions across cell membranes. ... Ion channels are protein pores that provide for the rapid movement of ions across cell membranes. Such channels control the ... and by allowing only specific types of ions to pass through (a property referred to as selectivity). Although ion channels have ...
... investigates sensory neuron ion channels called transient receptor potential (TRP) channels. The ion channel is found in large ... ONES Awardee Studies Ion Channels Activated by Environmental Irritants May 2, 2012 - ONES Awardee Studies Ion Channels ... but I wanted to know more about how to take an environmental health approach to studying these ion channels," he said. " ... The channel also appears to be involved in allergies and asthma. Jordt has found that mice modified to be deficient in the ...
By controlling ion permeability, ion channels at the membrane play a major role in regulating both electrical activity and ... Given the importance of ion channels in cell physiology, a knowledge of the structure and properties of these channels in the β ... analysis of ion channels in other tissues can now be applied to the isolation and characterization of the β-cell ion channels. ... Ion Channels and Insulin Secretion. Arun S Rajan, Lydia Aguilar-Bryan, Daniel A Nelson, Gordon C Yaney, Walter H Hsu, Diana L ...
Purchase Essential Ion Channel Methods - 1st Edition. Print Book & E-Book. ISBN 9780123822048, 9780123822376 ... 1. Assembly of Ion Channels. ZuFang Sheng and Carol Deutsch. PART II - Genetics. 2. Identification of Ion Channel-Associated ... Ion Channels As Tools to Monitor Lipid Bilayer-Membrane Protein Interactions: Gramicidin Channels As Molecular Force. O. S. ... Analysis of Ion Channel Associated Proteins. Michael Wyszynski and Morgan Sheng. 20. Secondary Messenger Regulation of Ion ...
Ion Channel. Sold by:Ion Channel Ion Channel Software Supply Chain Assurance and Logistics, Continuous Monitoring and SecDevOps ... Ion Channel Software Supply Chain Assurance and Logistics, Continuous Monitoring and SecDevOps GRC ...
Natural gates can be altered and augmented using synthetic chemistry and molecular biology to develop channels with completely ... Ion channels are gated by a variety of stimuli, including ligands, voltage, membrane tension, temperature, and even light. ... Engineering light-gated ion channels Biochemistry. 2006 Dec 26;45(51):15129-41. doi: 10.1021/bi0618058. Epub 2006 Dec 2. ... Ion channels are gated by a variety of stimuli, including ligands, voltage, membrane tension, temperature, and even light. ...
... and Therapeutic Approaches for Primary Cardiomyopathies of Gene Mutations Affecting Ion Channel Function Stephan E. Lehnart, ... Direct Inhibition of Cardiac Hyperpolarization-Activated Cyclic Nucleotide-Gated Pacemaker Channels by Clonidine Anne Knaus, ... Channels Tian Xue, Chung-Wah Siu, Deborah K. Lieu, Chu-Pak Lau, Hung-Fat Tse and Ronald A. Li ...
Glutamate receptor ion channels: structure, regulation, and function.. Traynelis SF1, Wollmuth LP, McBain CJ, Menniti FS, Vance ... Helical regions of the ion channel as well as parts of LBD that are proposed to move upon activation are shown as cylinders. ... The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels ... Data for GluA1 single-channel recordings were from , GluK2 single channel recordings were from , and GluN2B macroscopic current ...
... the researchers could see the charge state of working ion channels in living cells. They saw that, in anion-selective channels ... One mediates inhibition by channeling anions, or negatively charged ions, while the other mediates excitation by channeling ... "These channels are the subject of a lot of computational studies. Before this paper, if researchers had to model these channels ... Small Change Makes A Big Difference For Ion Channels. by Sam Savage ...
NEUROTR_ION_CHANNEL (PS00236). Accession PS00236 Integration. Neurotransmitter-gated ion-channel, conserved site (IPR018000) ...
... all depend on ion channels. This review discusses recent results in the converging fields of nociception and ion channel ... Ion channels of nociception.. McCleskey EW1, Gold MS.. Author information. 1. Vollum Institute, Oregon Health Sciences ... proton-gated channels, and (d) nociceptor-specific Na+ channels. ...
Neuronal Ion Channels RT2 Profiler PCR Array The Human Neuronal Ion Channels RT² Profiler PCR Array was developed to profile ... Neuronal Ion Channels RT2 Profiler PCR Array The Mouse Neuronal Ion Channels RT² Profiler PCR Array was developed to profile ... Neuronal Ion Channels RT2 Profiler PCR Array The Rat Neuronal Ion Channels RT² Profiler PCR Array was developed to profile ... Activated transmembrane ion channels allow ions into or out of cells. In neurons, these channels promote neurotransmission by ...
  • This study examined nine detergents upon nAChR solubilization and purification, to assess receptor lipid composition using GC (Gas Chromatography)-FID (Flame Ionization) and/or GC-MSD (Mass Selective Detectors), stability and aggregation state using A-SEC (Analytical Size-Exclusion Chromatography) and EM (Electron Microscopy), and planar lipid bilayers to measure ion channel function. (upr.edu)
  • The Acid-sensing Ion Channel (ASIC) detects changes in pH levels in the organism and transmits the pain signal to the brain. (scienmag.com)
  • 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. (unthsc.edu)
  • Current flow through the channel formed in planar phospholipid bilayer membranes by the PA 65 fragment of anthrax toxin is blocked, in a voltage-dependent manner, by tetraalkylammonium ions (at micromolar concentrations), which bind to a blocking site within the channel lumen. (elsevier.com)
  • Blaustein, RO & Finkelstein, A 1990, ' Diffusion limitation in the block by symmetric tetraalkylammonium ions of anthrax toxin channels in planar phospholipid bilayer membranes ', Journal of General Physiology , vol. 96, no. 5, pp. 943-957. (elsevier.com)
  • We have presented evidence that diffusion plays a significant role in the kinetics of blocking by tetrabutylammonium ion (Bu 4 N + ) from the cis (toxin-containing) side of the membrane (Blaustein, R. O., E. J. A. Lea, and A. Finkelstein. (elsevier.com)
  • Anapoe-C12E9 (Polyoxyethylene-(9)-dodecyl ether) and BigCHAP (N,N′-bis-(3-d- Gluconamidopropyl) cholamide) retained residual amounts of native lipid, maintaining moderate stability and ion channel function when compared to lipid-analog detergents. (upr.edu)
  • The research team identified through animal experiments that there is a different cell membrane merging mechanism between subunits of the Acid-sensing Ion Channel. (scienmag.com)
  • 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. (scienmag.com)
  • Professor Byung-Chang Suh from DGIST's Department of Brain and Cognitive Sciences said, 'Understanding of the cell membrane merging and activity control mechanism of the Acid-sensing Ion Channel plays an important role in identifying the pain signal transmission system. (scienmag.com)
  • Professor Byung-Chang Suh's research team from the Department of Brain and Cognitive Sciences succeeded in identifying a new operational mechanism principle of the 'Acid-sensing Ion Channel,' which recognizes internal pain in an organism. (scienmag.com)
  • 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. (scienmag.com)
  • That our study investigated a new control mechanism of the Acid-sensing Ion Channel has important implications. (scienmag.com)
  • Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking of ASIC2b via Heteromeric Assembly', Scientific Reports 2016. (scienmag.com)
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