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.

Molecular dynamics of the sodium channel pore vary with gating: interactions between P-segment motions and inactivation. (1/8527)

Disulfide trapping studies have revealed that the pore-lining (P) segments of voltage-dependent sodium channels undergo sizable motions on a subsecond time scale. Such motions of the pore may be necessary for selective ion translocation. Although traditionally viewed as separable properties, gating and permeation are now known to interact extensively in various classes of channels. We have investigated the interaction of pore motions and voltage-dependent gating in micro1 sodium channels engineered to contain two cysteines within the P segments. Rates of catalyzed internal disulfide formation (kSS) were measured in K1237C+W1531C mutant channels expressed in oocytes. During repetitive voltage-clamp depolarizations, increasing the pulse duration had biphasic effects on the kSS, which first increased to a maximum at 200 msec and then decreased with longer depolarizations. This result suggested that occupancy of an intermediate inactivation state (IM) facilitates pore motions. Consistent with the known antagonism between alkali metals and a component of slow inactivation, kSS varied inversely with external [Na+]o. We examined the converse relationship, namely the effect of pore flexibility on gating, by measuring recovery from inactivation in Y401C+E758C (YC/EC) channels. Under oxidative conditions, recovery from inactivation was slower than in a reduced environment in which the spontaneous YC/EC cross-link is disrupted. The most prominent effects were slowing of a component with intermediate recovery kinetics, with diminution of its relative amplitude. We conclude that occupancy of an intermediate inactivation state facilitates motions of the P segments; conversely, flexibility of the P segments alters an intermediate component of inactivation.  (+info)

Functional consequences of mutations in the human alpha1A calcium channel subunit linked to familial hemiplegic migraine. (2/8527)

Mutations in alpha1A, the pore-forming subunit of P/Q-type calcium channels, are linked to several human diseases, including familial hemiplegic migraine (FHM). We introduced the four missense mutations linked to FHM into human alpha1A-2 subunits and investigated their functional consequences after expression in human embryonic kidney 293 cells. By combining single-channel and whole-cell patch-clamp recordings, we show that all four mutations affect both the biophysical properties and the density of functional channels. Mutation R192Q in the S4 segment of domain I increased the density of functional P/Q-type channels and their open probability. Mutation T666M in the pore loop of domain II decreased both the density of functional channels and their unitary conductance (from 20 to 11 pS). Mutations V714A and I1815L in the S6 segments of domains II and IV shifted the voltage range of activation toward more negative voltages, increased both the open probability and the rate of recovery from inactivation, and decreased the density of functional channels. Mutation V714A decreased the single-channel conductance to 16 pS. Strikingly, the reduction in single-channel conductance induced by mutations T666M and V714A was not observed in some patches or periods of activity, suggesting that the abnormal channel may switch on and off, perhaps depending on some unknown factor. Our data show that the FHM mutations can lead to both gain- and loss-of-function of human P/Q-type calcium channels.  (+info)

Individual subunits contribute independently to slow gating of bovine EAG potassium channels. (3/8527)

The bovine ether a go-go gene encodes a delayed rectifier potassium channel. In contrast to other delayed rectifiers, its activation kinetics is largely determined by the holding potential and the concentration of extracellular Mg2+, giving rise to slowly activating currents with a characteristic sigmoidal rising phase. Replacement of a single amino acid in the extracellular linker between transmembrane segments S3 and S4 (L322H) strongly reduced the prepulse dependence and accelerated activation by 1 order of magnitude. In addition, compared with the wild type, the half-activation voltage of this mutant was shifted by more than 30 mV to more negative potentials. We used dimeric and tetrameric constructs of the bovine eag1 gene to analyze channels with defined stoichiometry of mutated and wild-type subunits within the tetrameric channel complexes. With increasing numbers of mutated subunits, the channel activation was progressively accelerated, and the sigmoidicity of the current traces was reduced. Based on a quantitative analysis, we show that the slow gating, typical for EAG channels, is mediated by independent conformational transitions of individual subunits, which gain their voltage dependence from the S4 segment. At a given voltage, external Mg2+ increases the probability of a channel subunit to be in the slowly activating conformation, whereas mutation L322H strongly reduces this probability.  (+info)

Voltage and calcium use the same molecular determinants to inactivate calcium channels. (4/8527)

During sustained depolarization, voltage-gated Ca2+ channels progressively undergo a transition to a nonconducting, inactivated state, preventing Ca2+ overload of the cell. This transition can be triggered either by the membrane potential (voltage-dependent inactivation) or by the consecutive entry of Ca2+ (Ca2+-dependent inactivation), depending on the type of Ca2+ channel. These two types of inactivation are suspected to arise from distinct underlying mechanisms, relying on specific molecular sequences of the different pore-forming Ca2+ channel subunits. Here we report that the voltage-dependent inactivation (of the alpha1A Ca2+ channel) and the Ca2+-dependent inactivation (of the alpha1C Ca2+ channel) are similarly influenced by Ca2+ channel beta subunits. The same molecular determinants of the beta subunit, and therefore the same subunit interactions, influence both types of inactivation. These results strongly suggest that the voltage and the Ca2+-dependent transitions leading to channel inactivation use homologous structures of the different alpha1 subunits and occur through the same molecular process. A model of inactivation taking into account these new data is presented.  (+info)

Gating connexin 43 channels reconstituted in lipid vesicles by mitogen-activated protein kinase phosphorylation. (5/8527)

The regulation of gap junctional permeability by phosphorylation was examined in a model system in which connexin 43 (Cx43) gap junction hemichannels were reconstituted in lipid vesicles. Cx43 was immunoaffinity-purified from rat brain, and Cx43 channels were reconstituted into unilamellar phospholipid liposomes. The activities of the reconstituted channels were measured by monitoring liposome permeability. Liposomes containing the Cx43 protein were fractionated on the basis of permeability to sucrose using sedimentation in an iso-osmolar density gradient. The gradient allowed separation of the sucrose-permeable and -impermeable liposomes. Liposomes that were permeable to sucrose were also permeable to the communicating dye molecule lucifer yellow. Permeability, and therefore activity of the reconstituted Cx43 channels, were directly dependent on the state of Cx43 phosphorylation. The permeability of liposomes containing Cx43 channels was increased by treatment of liposomes with calf intestinal phosphatase. Moreover, liposomes formed with Cx43 that had been dephosphorylated by calf intestinal phosphatase treatment showed increased permeability to sucrose. The role of phosphorylation in the gating mechanism of Cx43 channels was supported further by the observation that phosphorylation of Cx43 by mitogen-activated protein kinase reversibly reduced the permeability of liposomes containing dephosphorylated Cx43. Our results show a direct correlation between gap junctional permeability and the phosphorylation state of Cx43.  (+info)

Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1. (6/8527)

Small and intermediate conductance Ca2+-activated K+ channels play a crucial role in hyperpolarizing the membrane potential of excitable and nonexcitable cells. These channels are exquisitely sensitive to cytoplasmic Ca2+, yet their protein-coding regions do not contain consensus Ca2+-binding motifs. We investigated the involvement of an accessory protein in the Ca2+-dependent gating of hIKCa1, a human intermediate conductance channel expressed in peripheral tissues. Cal- modulin was found to interact strongly with the cytoplasmic carboxyl (C)-tail of hIKCa1 in a yeast two-hybrid system. Deletion analyses defined a requirement for the first 62 amino acids of the C-tail, and the binding of calmodulin to this region did not require Ca2+. The C-tail of hSKCa3, a human neuronal small conductance channel, also bound calmodulin, whereas that of a voltage-gated K+ channel, mKv1.3, did not. Calmodulin co-precipitated with the channel in cell lines transfected with hIKCa1, but not with mKv1. 3-transfected lines. A mutant calmodulin, defective in Ca2+ sensing but retaining binding to the channel, dramatically reduced current amplitudes when co-expressed with hIKCa1 in mammalian cells. Co-expression with varying amounts of wild-type and mutant calmodulin resulted in a dominant-negative suppression of current, consistent with four calmodulin molecules being associated with the channel. Taken together, our results suggest that Ca2+-calmodulin-induced conformational changes in all four subunits are necessary for the channel to open.  (+info)

Voltage sensors in domains III and IV, but not I and II, are immobilized by Na+ channel fast inactivation. (7/8527)

Using site-directed fluorescent labeling, we examined conformational changes in the S4 segment of each domain of the human skeletal muscle sodium channel (hSkM1). The fluorescence signals from S4 segments in domains I and II follow activation and are unaffected as fast inactivation settles. In contrast, the fluorescence signals from S4 segments in domains III and IV show kinetic components during activation and deactivation that correlate with fast inactivation and charge immobilization. These results indicate that in hSkM1, the S4 segments in domains III and IV are responsible for voltage-sensitive conformational changes linked to fast inactivation and are immobilized by fast inactivation, while the S4 segments in domains I and II are unaffected by fast inactivation.  (+info)

Distinct sensitivities of OmpF and PhoE porins to charged modulators. (8/8527)

The inhibition of the anion-selective PhoE porin by ATP and of the cation-selective OmpF porin by polyamines has been previously documented. In the present study, we have extended the comparison of the inhibitor-porin pairs by investigating the effect of anions (ATP and aspartate) and positively charged polyamines (spermine and cadaverine) on both OmpF and PhoE with the patch-clamp technique, and by comparing directly the gating kinetics of the channels modulated by their respective substrates. The novel findings reported here are (1) that the activity of PhoE is completely unaffected by polyamines, and (2) that the kinetic changes induced by ATP on PhoE or polyamines on OmpF suggest different mechanisms of inhibition. ATP induces a high degree of flickering in the PhoE-mediated current and appears to behave as a blocker of ion flow during its presumed transport through PhoE. Polyamines modulate the kinetics of openings and closings of OmpF, in addition to promoting a blocker-like flickering activity. The strong correlation between sensitivity to inhibitors and ion selectivity suggests that some common molecular determinants are involved in these two properties and is in agreement with the hypothesis that polyamines bind inside the pore of cationic porins.  (+info)

A vocal valve for connection to a tracheostoma comprises a filter (16) for moisture and heat exchange at breathing through the vocal valve, and a housing (15) receiving the filter and having a first opening at one side of the filter to be connected to the tracheostoma, and at least one second opening at the opposite side of the filter, which communicates with the surroundings. A manually operated valve element (15′) for blocking the air passage through the filter is constructed to close said first opening at manual operation thereof.
Voltage-gated ion channels play fundamental roles in neural excitability, they are for instance responsible for every single heart beat in our bodies, and dysfunctional channels cause disease that can be even lethal. Understanding how the voltage sensor of these channels function is critical for drug design of compounds targeting neuronal excitability.. The opening and closing of the pore in voltage-gated potassium (Kv) channels is caused by the arginine-rich S4 helix of the voltage sensor domain (VSD) moving in response to an external potential. In fact, VSDs are remarkably efficient at turning membrane potential into conformational changes, which likely makes them the smallest existing biological engines. Exactly how this is accomplished is not yet fully known and an area of hot debate, especially due to the lack of structures of the resting and intermediate states along the activation pathway. In this thesis I study how the VSD activation works and show how toxic compounds modulate channel ...
Ion channel conductance can be influenced by electrostatic effects originating from fixed surface charges that are remote from the selectivity filter. To explore whether surface charges contribute to the conductance properties of Kir2.1 channels, unitary conductance was measured in cell-attached recordings of Chinese hamster ovary (CHO) cells transfected with Kir2.1 channels over a range of K + activities (4.6-293.5 mM) using single-channel measurements as well as nonstationary fluctuation analysis for low K + activities. K + ion concentrations were shown to equilibrate across the cell membrane in our studies using the voltage-sensitive dye DiBAC 4 (5). The dependence of γ on the K + activity (a K ) was fit well by a modified Langmuir binding isotherm, with a nonzero intercept as a K approaches 0 mM, suggesting electrostatic surface charge effects. Following the addition of 100 mM N-methyl-D-glucamine (NMG + ), a nonpermeant, nonblocking cation or following pretreatment with 50 mM ...
In this study, we found that mutation E219R shifts Q-V relationship leftwards by 126 mV at 0 Ca2+ compared with WT and changes slope factor from 50 to 38 mV, indicating an increase of gating charge (Fig. 1A,B). In addition to the direct effects on voltage sensor movements, the mutation also shifts G-V relationship rightwards at 0 Ca2+ and increases Ca2+ sensitivity (Fig. 1C-F), which are the results of an electrostatic interaction between E219R and E321/E324 (Figs. 2 and 3) that alters the coupling among the activation gate, voltage sensor, and Ca2+ binding (Fig. 4; Table 2).. Ion channels often contain distinct structural domains for sensing physiological stimuli and the pore-activation gate. The coupling among these domains during channel activation is an important molecular process that has not been fully understood. One basic question is as follows: what kind of changes in the properties of channel function would indicate a change of coupling? It has been elegantly shown that, in ...
Latest Job Opening at Pyramids Diagnostics Services for Nurse/Health Assistant in , Nigeria for job seekers and professionals. Apply today
Na Channel Has a quick onset and quickly turns off: inactivating channel. K is the opposite with slow onset and slow turn off: noninactivating channel. This difference is caused by differences in the two proteins. The Na channel has two gates: the activation gate and the inactivation gate. The activation gate is sensitive to the potential. When the activation gate is closed the inactivation gate is closed. When the inside of the cell is depolarized, the activation gate quickly opens. The inactivation gate, composed of negative proteins, slowly is repelled by the positive change in the intracellular environment, so it closes the channel by find its way into the pore of the channel.. K Channel. Has a single gate activated by the membrane potential, so it will stay open all the time the membrane has a certain potential. Na and K Conductances Nas conductance is characterized by a rapid onset and a rapid offset. Ks conductance is characterized by a slow onset and a slow offset. Membrane potential ...
A device for the uniform dosing of an amount of faeces onto reagent paper for the detection of a component material in the faeces. The device comprises test paper and a template disposed thereover having a given thickness and comprising at least one set of two superposed openings of any desired shape. Each set of openings includes a first opening and a second opening disposed between the first opening and the test paper and having a larger area than and encompassing the area of the first opening.
A coordinate measuring system having a quick disconnect is disclosed. The coordinate measuring system includes a multijointed arm having a first end and a plurality of transfer housings for generating signals indicating the position of the first end. A first locking device is mountable to a second end of the arm. The first locking device has a first surface which is removably received within a first opening in a housing. The housing is mountable to a support and includes a second opening for communicating with the first opening. A second locking device having a second surface is movably received within the second opening from an unlocked position to a locked position and constitutes a cam which rotates to engage the first locking device. The second surface engages the first surface in the locked position to prevent the first locking member from being removed from the first opening. The first and second surfaces are not engaged in the unlocked position so that the first locking member can be removed from
A method and system are disclosed for enabling point-to-point and multicast communication in a multiple access network using three types of communication channels, namely, one or more upstream payload channels, one or more upstream control channels and one or more downstream channels. Each channel illustratively is divided into slots or mini-slots. Each upstream payload channel is assigned for carrying upstream directed payload bitstreams from stations to a central controller. The central controller has an independent receiver for each upstream channel for simultaneous reception of control and payload bitstreams. Each station has at least one frequency agile programmable transmitter for sequential transmission of control and payload bitstreams or separate upstream control and payload channel transmitters, respectively, for simultaneous transmission of control and payload bitstreams. Each upstream control channel is assigned for carrying upstream directed control bitstreams, such as reservation request
Michael K. 44 years old, Nationality - German. I had -5.00 diopters of Nearsightedness before my smile treatment 1 week ago. Waking up in the morning without searching for my glasses is a perfect feeling! For the first time in 35 years I can open my eyes and see clearly. Playing sport without my glasses/lenses is also much more convenient. I am very satisfied with the professional expertise and service I received at EuroEyes.. ...
The above discussion suggests that the inner vestibule would be large enough for sugars to enter. On this basis, the presence of sugars in the vestibule would be expected to interfere with the passage of K+ from the intracellular bulk solution through the vestibule to the selectivity filter. Our data support this conclusion. For sucrose ≤1 M, glycerol and glucose ≤2 M, and for voltages ≤200 mV, diffusion-limited currents were not observed, yet sugars still reduced the unitary currents (Figs. 1 and 2). Because the diffusion of K+ from the bulk solution into the vestibule was not rate limiting for these experiments, then these observations suggest that sugars are entering the vestibule and slowing the transit of K+ through the vestibule to the selectivity filter.. Sugars within the vestibule would reduce the effective area available for diffusion through the vestibule. An empirical model that assumed that the fractional reduction of outward current was proportional to the fractional volume ...
CiteSeerX - Scientific articles matching the query: Side Channel Analysis of Practical Pairing Implementations: Which Path Is More Secure?
Archaeal TRIC family homologue of 205 aas and 7 TMSs. In animals, Ca2+ release from the sarcoplasmic reticulum (SR) or endoplasmic reticulum (ER) is crucial for muscle contraction, cell growth, apoptosis, learning and memory. The eukaryotic TRIC channels are cation channels balancing the SR and ER membrane potentials, and are implicated in Ca2+ signaling and homeostasis. Kasuya et al. 2016 presented crystal structures of two prokaryotic TRIC channels in the closed state and conducted structure-based functional analyses of these channels. Each trimer subunit consists of seven TMSs with two inverted 3 TMS repeats (Silverio and Saier 2011). The electrophysiological, biochemical and biophysical analyses revealed that TRIC channels possess an ion-conducting pore within each subunit, and that trimer formation contributes to the stability of the protein. The symmetrically related TMS2 and TMS5 helices are kinked at conserved glycine clusters, and these kinks are important for channel activity. The ...
To describe the [K+]ext and voltage dependence of Po at depolarized voltages, we developed a series of kinetic schemes in which both K+ binding and hyperpolarization are coupled to relative energetic stabilization of the open-conductive state over the open-inactivated state. Rate constants and voltage dependences for transitions among conductive and inactivated states in the schemes were constrained by two-dimensional distributions of adjacent open and closed dwell-times obtained over a range of [K+]ext and voltage for each channel (Rothberg and Magleby, 1998, 1999, 2000). Schemes were ranked statistically after applying a penalty for increasing the number of free parameters in a scheme, according to Eq. 6.. We took the approach of fitting the simplest scheme, with one open-conductive (O) and one open-inactivated (I) state, and then adding additional states (O or I) until a further addition yielded no significant improvement in the maximum likelihood value for the scheme. For each scheme, we ...
A balloon dilation catheter comprising a tubular member having a proximal end and a distal end. An inflatable balloon is disposed at the distal end of the tubular member. A first lumen is disposed in the tubular member and in is communication with an interior of the inflatable balloon. A second lumen is disposed in the tubular member for receiving a guidewire substantially along a portion of its length. The second lumen has a first opening in the proximal region of the tubular member and a second opening at the distal region of the tubular member. A first slit is disposed longitudinally in the tubular member and extends along at least a portion of the tubular member, the first slit comprising a first pair of longitudinal edges in a side by side relationship. The tubular member is constructed of a resilient material such that, as the guidewire is separated from the second lumen, the longitudinal edges are biassed open from a first position to a second position having a gap greater than or equal a
A modular fluid heating apparatus may be assembled from a plurality of modular heating components. Each modular heating component includes a first molded section defining a first opening therethrough and a second molded section defining a second opening therethrough. The molded sections are mated and define an enclosed area between the molded sections. The first and second openings are aligned to form a fluid tight passage through the modular heating component. A resistance heating element is secured between the first and second molded sections in the enclosed area. The resistance heating element includes a supporting substrate having a first surface thereon and an electrical resistance heating material fastened to the first surface of the supporting substrate. The resistance heating material forms a predetermined circuit path having a pair of terminal end portions fixed to a pair of electrical connectors. The modular heating components are sealably mated to define a fluid collection area between
A high-speed race awaits guests this summer when Wet ‘n Wild Orlando opens Florida’s tallest and fastest water-based racing attraction of its kind.
2017, VegasNews.com. All rights reserved. All content copyrighted or used with permission. All rights reserved. This content may not be distributed, modified, reproduced in whole or in part without prior permission from VegasNews.com ...
Solidarités International (SI) is a French humanitarian organisation operating for over 35 years who is committed to providing aid in the event of
Hi all, posting a book here: My Windows 7 Ultimate 64 bit does not seem to open any 32 bit programs. When I try to open a 32 bit program, it shows up in the task manager for a few seconds (e.g. firefox.exe x32), then disappears after a few seconds. I can open Internet Explorer 64 bit fine, run it with no programs, but the 32 bit version doesnt work. I also cant access many of the Windows control panel settings, such as Uninstall Programs. I can open the Control Panel folder, but
Four years ago, James Larrimore didnt give a second thought to putting on a pair of pants or taking a shower. Then came the mulching machine accident in which he lost his left arm.Since then, Mr.
Find channel gate articles on Environmental XPRT, the worlds largest environmental industry marketplace and information resource.
My pool builder opened our pool about a month ago. As the pool was built late last summer, its the first opening weve had. Pool builder says he typically adds sequestriant when he opens his pools. Well when he came out last month, he didnt have the sequestriant with him and said he would drop it by the house. I figured it couldnt hurt to add it when I received it. Cut to today, where I have everything fairly well dialed in (I have a SWG): FC 5 pH 7.6 TA 80 Calcium 240 CYA 40 (still
Introducing myself -- an old newbie. Bought a house 2 years ago with an inground pool. Never owned or managed a pool before. First year, first opening, what a mess, too many trees near the uncovered pool. lots of vacuuming, scooping, bleach, backwashing, etc. Finally got into a routine, about 4 gallons a week. Then got the Del Ozonator, then the FloatTron, down to one gallon a week. Installed a new timer for the pump so that it didnt run 24/7, and had a leak (pool light) fixed. Next
Each α subunit - hence also Nav1.7 - is composed of four homologous domains (DI-DIV), with each domain consisting of six transmembrane segments (S1-S6), with S4 acting as a voltage-sensor and S5 and S6 lining the pore [815]. Structural modellings approach of Nav1.7 have identified an aromatic residue within the cytoplasm-proximal portion of each of the pore-lining S6 helices that were predicted to form a hydrophobic ring at the cytoplasmic end of the pore that stabilizes the channels pre-open state. This element is predicted to raise the energy barrier for the movement of S6, which is necessary to open the channels pore, thus stabilizing the closed or pre-open state of the channel [1419][1420]. ...
Network Forgetting a new co-workers name is a common problem, but admitting it openly is a surprisingly welcomed solution, and it can open the door to positive rapport. Eric Cai writes more from his experience.. ...
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.
Thank you for sharing this Molecular Pharmacology article.. NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.. ...
TY - JOUR. T1 - Hypoxia modulates nitric oxide-induced regulation of NMDA receptor currents and neuronal cell death. AU - Gbadegesin, Muyiwa. AU - Vicini, Stefano. AU - Hewett, Sandra. AU - Wink, David A.. AU - Espey, Michael. AU - Pluta, Ryszard M.. AU - Colton, Carol A.. PY - 1999. Y1 - 1999. N2 - Nitric oxide (NO) released from a new chemical class of donors enhances N-methyl-D-aspartate (NMDA) channel activity. Using whole cell and single- channel patch-clamp techniques, we have shown that (Z)-1-[N(3-ammoniopropyl)- N-(n-propyl)amino]-NO (PAPA-NO) and diethylamine NO, commonly termed NONOates, potentiate the glutamate-mediated response of recombinant rat NMDA receptors(NR1/NR2A) expressed in HEK-293 cells. The overall effect is an increase in both peak and steady-state whole cell currents induced by glutamate. Single-channel studies demonstrate a significant increase in open probability but no change in the mean single-channel open time or mean channel conductance. Reduction in oxygen levels ...
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. ...
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 ...
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.. ...
A system that stores a color management transform, typically using a grid table, where one or more of the input channels represents parameters used to control the reproduction of the conventional color image channels. The invention augments the existing grid-table based transform structure with additional channels to control the operation of the color models involved. These additional channels are not the conventional calorimetric or colorant image channels such as red, green, and blue, but are to control other aspects of the color transformation, such as exposure level or saturation. The augmentation also includes identification information that identifies the type of control (exposure, grey component replacement, etc.) the extra channels provide.
The gating of voltage-gated ion channels is controlled by the arginine-rich S4 helix of the voltage-sensor domain moving in response to an external potential. Recent studies have suggested that S4 moves in three to four steps to open the conducting pore, thus visiting several intermediate conformations during gating. However, the exact conformational changes are not known in detail. For instance, it has been suggested that there is a local rotation in the helix corresponding to short segments of a 3(10)-helix moving along S4 during opening and closing. Here, we have explored the energetics of the transition between the fully open state (based on the X-ray structure) and the first intermediate state towards channel closing (C-1), modeled from experimental constraints. We show that conformations within 3 angstrom of the X-ray structure are obtained in simulations starting from the C-1 model, and directly observe the previously suggested sliding 3(10)-helix region in S4. Through systematic free ...
Correlations between the voltage-gated ion channels shal (A-C), CbNav (D-F), and shaker (G-I) and soma size, actin, and tubulin expression. Points represe
Voltage-gated potassium (KV) channels open in response to membrane depolarization and are present in many cell types. In excitable cells, KV channels serve as the primary mechanism of repolarization of action potentials, whereas in nonexcitable cells, KV channels control the cell resting potential. Given the role of KV channels, it is not surprising that they regulate many fundamental physiological processes and are therefore considered important therapeutic targets for treatment of autoimmune, metabolic, neurological, and cardiovascular disorders, as well as cancer (Wulff et al., 2009). Despite these facts, there has been limited success in the clinical development of therapeutic agents that target KV channels. One reason for this is that many of the small molecules identified to date lack true molecular selectivity across members of the KV and other ion channel families, which could significantly compromise their therapeutic index. The lack of ion channel selectivity seems to be due to binding ...
sick unanticipated rewards will quickly keep a download voltage-gated ion channels as drug targets (methods and principles in medicinal psychotherapy teamwork. We get included with Bookshout and evaluate investigating their couple as a happy outcry to honor our signs. Their App brings full-throated for sight on funds and heavenly types.
Some characteristic features of band structures, like the band degeneracy at high symmetry points or the existence of energy gaps, usually reflect the symmetry of the crystal or, more precisely, the symmetry of the wave vector group at the relevant points of the Brillouin zone. In this paper, we will illustrate this property by considering two-dimensional (2D)-hexagonal lattices characterized by a possible two-fold degenerate band at the K points with a linear dispersion (Dirac points). By combining scanning tunneling spectroscopy and angle-resolved photoemission, we study the electronic properties of a similar system: the Ag/Cu(111) interface reconstruction characterized by a hexagonal superlattice, and we show that the gap opening at the K points of the Brillouin zone of the reconstructed cell is due to the symmetry breaking of the wave vector group.
Voltage-dependent ion channels are gated by voltage sensors that show a switchlike response to voltage differences across the membrane. Tao et al. used mutagenesis, electrophysiology, and x-ray crystallography to gain insight into the molecular basis of this response in voltage-dependent potassium channels. An occluded site was identified that catalyzes translation of positive charges across the membrane. The closed channel appears to be associated with a distribution of conformations, depending on the degree of hyperpolarization of the membrane, whereas the open channel appears to be associated with a specific conformation. Thus, the transition of the ion channel from open to closed occurs over a very small voltage difference.. X. Tao, A. Lee, W. Limapichat, D. A. Dougherty, R. MacKinnon, A gating charge transfer center in voltage sensors. Science 328, 67-73 (2010). [Abstract] [Full Text] ...
101年公務人員特種考試關務人員考試、101年公務人員特種考試 移民行政人員考試及101年國軍上校以上軍官轉任公務人員考試試題 代號:11130 等 別: 三等關務人員考試 類(科)別: 藥事 科 目: 藥理學與藥物化學 一、請說明下列各專有名詞之異同處。(20 分) (一) Antagonist & Inverse agonist (二) Pharmacodynamic & Pharmacokinetic (三) Ligand-gated channels & Voltage-gated channels (四) Ionotropic receptors & Metabotropic receptors (五) Tachyphylaxis & Supersensitivity ...
TY - JOUR. T1 - Voltage-Dependent Inactivation of MscS Occurs Independently of the Positively Charged Residues in the Transmembrane Domain. AU - Nomura, Takeshi. AU - Sokabe, Masahiro. AU - Yoshimura, Kenjiro. PY - 2016. Y1 - 2016. N2 - MscS (mechanosensitive channel of small conductance) is ubiquitously found among bacteria and plays a major role in avoiding cell lysis upon rapid osmotic downshock. The gating of MscS is modulated by voltage, but little is known about how MscS senses membrane potential. Three arginine residues (Arg-46, Arg-54, and Arg-74) in the transmembrane (TM) domain are possible to respond to voltage judging from the MscS structure. To examine whether these residues are involved in the voltage dependence of MscS, we neutralized the charge of each residue by substituting with asparagine (R46N, R54N, and R74N). Mechanical threshold for the opening of the expressed wild-type MscS and asparagine mutants did not change with voltage in the range from -40 to +100 mV. By contrast, ...
Compare sodium voltage-gated channel alpha subunit 8 Biomolecules from leading suppliers on Biocompare. View specifications, prices, citations, reviews, and more.
NMDARs retained in circulating RBCs remain functional and keep responding to stimulation with glutamate, HCA, or NMDA as well as to the inhibition by MK-801 (Figs. 3-6). Calcium transport through the receptor is electrogenic, putting NMDARs in line with other calcium-transporting ion channels (Fig. 4). The number of such ion channels in RBC is rather limited and their molecular identity often remains unknown (28). Among the TRP channels, only TRPC6 is described in RBC (17). Furthermore, there is biochemical and functional evidence for a CaV2.1 channel (1, 71). There are numerous electrophysiological reports of Ca2+-permeable channels that can be grouped in two categories: nonselective voltage activated cation channels (NSVAC; e.g., Refs. 4, 29) and receptor-mediated channels (e.g., Refs. 13, 25). Although the I-V curve for NSVAC in whole cell conductance mode (55) differs from that shown in Fig. 4D, NMDARs and NSVACs have one common property. Both channels share the hysteresis of whole cell ...
... and Cobalt 10 are offered as a base console with 5000 control channels and 4,096 outputs (8 universes of DMX512A). A single control channel may control only intensity (dimmers) or it may control a DMX-controlled device (moving light, LED, media server, etc ...
Adenoviral i-eag domains restored slow deactivation in hiPSC-CMs.Representative tail currents recorded from hiPSC-CMs infected by: A, WT hERG1a.Ad; B, hERG1a(R5
... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
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. ...
An apparatus for establishing a re-usable, recurring, mechanical connection to an organ within a patient is provided. A body fluid cartridge exchange platform device includes a hollow cartridge platform housing with a first end having an opening. The platform housing can additionally have a second end with a second opening. The first opening and the second opening facilitate insertion of an exchange cartridge insert that sealably engages the housing. The first opening and the second opening additionally facilitate removal of the exchange cartridge insert. The exchange cartridge insert can facilitate a flow path between a first leg and a second leg of the platform housing, and can facilitate a flow path between the platform housing and an external location for medical procedure or drug delivery purposes.
A pressure swing sorption system comprises first and second sorbing chambers each including first and second openings defining a gas flow path between them, a sorbent bed disposed in the gas flow path and having a sorption inlet region near the first opening, and a heater positioned near the sorption inlet region of the sorbent bed. A valve arrangement interconnects an intake, an exhaust, and the first openings of the first and second sorbing chambers and also interconnects an outlet and the second openings of the first and second sorbing chambers. A connecting apparatus connects an energy source external to the first and second sorbing chambers to the heaters of the first and second sorbing chambers. A controller coupled to the valve arrangement and the connecting apparatus simultaneously directs gas from the first sorbing chamber to the outlet and directs a portion of the outlet gas through the second sorbing chamber to the exhaust. The controller also provides energy from the energy source to the
Structural model of hERG channels. (a) Key elements of hERG channel topology illustrated using the X-ray structure of KvAP. Two of the four subunits comprising the tetrameric channel are shown. (b) Model of the pore portion of hERG channel. The P-S6 fragment is shown for a dimer. Aromatic residues Phe656 and Tyr652 are critical for hERG block by most known small molecule ligands. Polar residues Thr623 and Ser624 modulate the binding potency for a number of reported hERG blockers ...
Ligand-gated ion channel. *Purinergic receptor. Enzyme-linked receptor. *Serine/threonine-specific protein kinase ...
cyclic nucleotide-gated ion channels. cGMP (vision), cAMP and cGTP (olfaction). Na+, K+ [11]. ... and ion channels.. Receptor proteins can be classified by their location. Transmembrane receptors include ion channel-linked ( ... 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 ...
GABAA receptors are ligand-gated ion channels (also known as ionotropic receptors); whereas GABAB receptors are G protein- ... Johnston GA (September 1996). "GABAc receptors: relatively simple transmitter -gated ion channels?". Trends Pharmacol. Sci. 17 ... Chebib M, Johnston GA (April 2000). "GABA-Activated ligand gated ion channels: medicinal chemistry and molecular biology". J. ... Fast-responding GABA receptors are members of a family of Cys-loop ligand-gated ion channels.[7][8][9] Members of this ...
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/ ...
Ion channels and Gates. *Gap junction Proteins. *G protein coupled receptors (e.g., Beta-adrenergic receptor) ... IMPs include transporters, linkers, channels, receptors, enzymes, structural membrane-anchoring domains, proteins involved in ... while type IV consists of several different polypeptides assembled together in a channel through the membrane. Type V proteins ...
cyclic nucleotide-gated ion channels. cGMP (vision), cAMP and cGTP (olfaction). Na+, K+ [11]. ... and ion channels. Receptor proteins can be classified by their location. Transmembrane receptors include ion channel-linked ( ... Type 1: Ligand-gated ion channels (ionotropic receptors) - These receptors are typically the targets of fast neurotransmitters ... This is seen with ion channel receptors.. *Uncoupling of the receptor effector molecules is seen with G-protein couple receptor ...
The nAChRs are ligand-gated ion channels, and, like other members of the "cys-loop" ligand-gated ion channel superfamily, are ... "Structural changes during ion channel gating". Trends Neurosci. 27 (6): 298-302. doi:10.1016/j.tins.2004.04.004. PMID 15165732 ... The nicotine ACh receptor is also a Na+, K+ and Ca2+ ion channel. Muscarinic acetylcholine receptors (mAChR, also known as " ... In contrast, the mAChRs are not ion channels, but belong instead to the superfamily of G-protein-coupled receptors that ...
Collingridge GL, Olsen RW, Peters J, Spedding M (2009). "A nomenclature for ligand-gated ion channels". Neuropharmacology. 56 ( ... The ion channel formed by kainate receptors is permeable to sodium and potassium ions. The single channel conductance of ... "The glutamate receptor ion channels" (abstract). Pharmacol. Rev. 51 (1): 7-61. PMID 10049997. ... kainate receptor channels is similar to that of AMPA channels, at about 20 pS. However, rise and decay times for postsynaptic ...
Collingridge GL, Olsen RW, Peters J, Spedding M (January 2009). "A nomenclature for ligand-gated ion channels". ... Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are activated by the neurotransmitter glutamate. ... NMDA receptors are blocked by magnesium ions and therefore only permit ion flux following prior depolarisation. This enables ... that forms the ion channel, and an intracellular C-terminal domain (CTD). AMPA receptors: GluA1/GRIA1; GluA2/GRIA2; GluA3/GRIA3 ...
Garcia ML (July 2004). "Ion channels: gate expectations". Nature. 430 (6996): 153-5. Bibcode:2004Natur.430..153G. doi:10.1038/ ... ion channels and ion pumps. Both pumps and channels are integral membrane proteins that pass through the bilayer, but their ... In contrast to ion pumps, ion channels do not build chemical gradients but rather dissipate them in order to perform work or ... All ion pumps have some sort of trigger or "gating" mechanism. In the previous example it was electrical bias, but other ...
M. L. Garcia."Ion channels: Gate expectations." Nature. 430. (2004) 153-155. T. J. McIntosh and S. A. Simon."Roles of Bilayer ... Bilayer mechanical properties have also been shown to alter the function of mechanically activated ion channels. Since lipid ... "Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers." Nature. 6996. (2004) 235-240. D ...
Catterall, WA; Cestele, S; Yarov-Yarovoy, V; Yu, FH; Konoki, K; Scheuer, T (2007). "Voltage-gated ion channels and gating ... which most likely acts by prolonging the inactivation of voltage-gated sodium channels (NaV channels). Cangitoxin is a ... Sea anemone toxins act on voltage-gated sodium channels (NaV1.1, NaV1.2, NaV1.4, NaV1.5, NaV1.6, NaV1.7) and depending on their ... According to its sequence homology, it is likely that cangitoxin prolongs the inactivation of the voltage-gated sodium channels ...
Catterall WA, Cestèle S, Yarov-Yarovoy V, Yu FH, Konoki K, Scheuer T (February 2007). "Voltage-gated ion channels and gating ... Since all potassium channels share the same ion conducting outer pore structure, Lq2 binds to all three potassium channel types ... It blocks various potassium channels, among others the inward-rectifier potassium ion channel ROMK1. Lq2 is also known as ... of the ROMK1 ion channel. It blocks the channel, binding in a 1:1 stoichiometric ratio with its β-sheet. Potential use of Lq2 ...
"Voltage-gated ion channels and gating modifier toxins". Toxicon. 49 (2): 124-41. doi:10.1016/j.toxicon.2006.09.022. PMID ... It is classified into Type I voltage-gated sodium channel neurotoxins. As reported by Norton et al., this group consists of ... AETX refers to a group of polypeptide neurotoxins isolated from the sea anemone Anemonia erythraea that target ion channels, ... sea anemone sodium channel inhibitory subfamily 1 and binds to the neurotoxin receptor site 3 of voltage-gated sodium channels ...
Price MP, Thompson RJ, Eshcol JO, Wemmie JA, Benson CJ (2004). "Stomatin modulates gating of acid-sensing ion channels". J. ... Acid-sensing ion channel 3 (ASIC3) also known as amiloride-sensitive cation channel 3 (ACCN3) or testis sodium channel 1 (TNaC1 ... "PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current". J. Biol. Chem. 279 ... "PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current". J. Biol. Chem. 279 ...
"Voltage-gated ion channels and gating modifier toxins". Toxicon. 49 (2): 124-41. doi:10.1016/j.toxicon.2006.09.022. PMID ... January 1989). "Modification of Na channel gating by an alpha scorpion toxin from Tityus serrulatus". J. Gen. Physiol. 93 (1): ... located on domain IV of the sodium channel, and thereby slow the inactivation of sodium channels. This toxin is active against ... does not discriminate between tissue-specific sodium channel subtypes and has been found to effect sodium channels from rat ...
"Voltage-gated ion channels and gating modifier toxins". Toxicon. 49 (2): 124-141. doi:10.1016/j.toxicon.2006.09.022. Duval, ... act upon sodium channels via binding to the channels' receptor site 3, which normally affects the channels' ability to ... The combination of poneratoxin binding to a cell membrane (in order to act upon a voltage-gated sodium channel) and the ... It prevents inactivation of voltage gated sodium channels and therefore blocks the synaptic transmission in the central nervous ...
2008 May;16(5):747-54 3. Catterall WA et al., Voltage-gated ion channels and gating modifier toxins. Toxicon. 2007 Feb;49(2): ... KTX binds to the Kv1.3 voltage-gated potassium channel and the Calcium-activated potassium channels (BK channels). (Lange A et ... through the Kv1.3 voltage-gated potassium channel and calcium-activated potassium channels by physically blocking the channel- ... Computational simulations of interactions of scorpion toxins with the voltage-gated potassium ion channel. Biophys J. 2004 Jun; ...
Voltage-gated ion channels and gating modifier toxins. Toxicon, 49(2), 124-141, Goudeta C., Chib C.-W., Tytgat J. (2002). An ... By blocking the inactivation of sodium ion channels, α-scorpion toxins prolong action potentials. Bukatoxin (short names: ... Other residues that could contribute to the binding of bukatoxin to the neurotoxin receptor site 3 of the sodium channels are ... It can be further categorized as a polypeptide gating modifier toxin that belongs to the α-subfamily of scorpion neurotoxins. ...
... with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel)". Biochem. J. 361 (Pt ... with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel)". Biochem. J. 361 (Pt ... Acid-sensing ion channel 1 (ASIC1) also known as amiloride-sensitive cation channel 2, neuronal (ACCN2) or brain sodium channel ... Price MP, Thompson RJ, Eshcol JO, Wemmie JA, Benson CJ (2005). "Stomatin modulates gating of acid-sensing ion channels". J. ...
Soon after, the role of cNMP in gated ion channels of chemosensitive cilia of olfactory sensory neurons was reported by Tadashi ... Kaupp UB, Seifert R (July 2002). "Cyclic nucleotide-gated ion channels". Physiol. Rev. 82 (3): 769-824. doi:10.1152/physrev. ... In 1992 Lawrence Haynes and King-Wai Yau uncovered cNMP's role in the light-dependent cyclic-nucleotide-gated channel of cone ... They have been identified as secondary messengers in both hormone and ion-channel signalling in eukaryotic cells, as well as ...
Binds to the α2δ-1 subunit of voltage gated calcium ion channels in the spinal cord. May also modulate NMDA receptors and ... Some novel and investigational analgesics include subtype-selective voltage-gated sodium channel blockers such as funapide 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 ...
"Nicotinic acetylcholine receptor superfamily of ligand-gated ion channels". Biochemistry. 29 (50): 11009-11023. ISSN 0006-2960 ...
This receptor functions as a ligand-gated ion channel. Several characteristic motifs of ATP-gated channels are present in its ... "Entrez Gene: P2RX5 purinergic receptor P2X, ligand-gated ion channel, 5". North RA (2002). "Molecular physiology of P2X ...
2005). "Stomatin modulates gating of acid-sensing ion channels". J. Biol. Chem. 279 (51): 53886-91. doi:10.1074/jbc.M407708200 ...
Disturbances in neuromodulatory processes acting on ion channels, receptors, and second messengers have been associated with ... voltage gated calcium channels become activated and calcium is able to flow into the cell which usually leads to the release of ... The channels are regulated by G protein-coupled receptors that can activate or inhibit the NALCN channels depending on the ... Other potassium channels like large conductance calcium-dependent potassium channels and sodium chloride dependent potassium ...
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 ...
The voltage-gated ion channel family includes voltage-gated sodium channels, voltage-gated calcium channels, and voltage-gated ... Ion channels are found in all cell types throughout the body, and have a wide variety of structures and functions. Ion channels ... Thus, ion channels typically are classified into one of two large groups based on the stimuli that activate them: voltage-gated ... The opening and closing (gating) of ion channels is controlled either by changes in membrane potential( voltage (Vacher et al ...
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 ...
Neurotransmitter-gated ion-channel transmembrane domain superfamily (IPR036719). *Neurotransmitter-gated ion-channel ligand- ... Neurotransmitter ligand-gated ion channels are transmembrane receptor-ion channel complexes that open transiently upon binding ... Neurotransmitter-gated ion-channel (IPR006201). Short name: Neur_channel Overlapping homologous superfamilies * ... Neurotransmitter-gated ion-channel (IPR006201) *5-hydroxytryptamine 3 receptor (IPR008132). *Gamma-aminobutyric acid A receptor ...
... chrissy chrissy_4u2c at hotmail.com Thu Oct 30 07:30:23 EST 2003 *Previous message: UV laser for DNA ... And how does that relate to ligand-gated channels in general? *Previous message: UV laser for DNA-protein cross-linking ... With a multisubunit ion channel, where the subunits have multiple transmembrane helices, how do you tell which of a subunits ...
... artificially light-responsive ion channels can facilitate experimental manipulation, allowing neuro ... As ion channels influence many aspects of biology, ... Light-gated ion channels. BioPhotonics. Feb 2007 As ion ... Because neurons use ion channels to transmit sensory information, light-gated ion channels could restore the senses of those ... Light-gated ion channels could deliver drugs to target tissues, and light could trigger the channels to expand, allowing for ...
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. ...
Ion channels are desirable therapeutic targets, yet ion channel-directed drugs with high selectivity and few side effects are ... Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation.. Danquah W1, Meyer-Schwesinger C2, Rissiek B1,3, ... P2X7 is a ligand-gated ion channel that, upon sensing adenosine 5-triphosphate released by damaged cells, initiates a ... Our results show that nanobody technology can generate potent, specific therapeutics against ion channels, confirm P2X7 as a ...
Pentameric ligand-gated ion channels (pLGICs) are key players in the early events of electrical signal transduction at chemical ... resolution and provides an important model system for the investigation of the general mechanisms of ion permeation and gating ... resolution and provides an important model system for the investigation of the general mechanisms of ion permeation and gating ... The family codes for a structurally conserved scaffold of channel proteins that open in response to the binding of ...
... voltage-gated ion channels directionally propagate electrical signals. Voltage-gated ion-channels are usually ion-specific, and ... DB Voltage-gated ion channel subunits The IUPHAR Compendium of Voltage-gated Ion Channels 2005 Voltage-Dependent Anion Channels ... Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the ... polycystin cation channels, glutamate-gated ion channels, calcium-dependent chloride channels, monovalent cation:proton ...
... ligand-gated ion channels, mechanosensitive ion channels, and temperature-gated ion channels. Most light-gated ion channels ... Light-gated ion channels are a family of ion channels regulated by electromagnetic radiation. Other gating mechanisms for ion ... Other types of gated ion channels, ligand-gated and voltage-gated, have been synthesized with a light-gated component in an ... Light-gated ion channels function in a similar manner to other gated ion channels. Such transmembrane proteins form pores ...
Structures: Neurotransmitter-gated ion-channel transmembrane domain (IPR006029). PDBe. The Protein Data Bank (PDB) is a ...
... ion channels are activated by cAMP or cGMP, crucial intracellular messenger molecules that regulate a wide variety of ... gated ion channels. Physiological Review 82(3): 769-824. Matulef K and Zagotta WN (2003) Cyclic nucleotide‐gated ion channels. ... Gating is the process by which ion channels open and close to control the flow of ions. ... Cyclic Nucleotide‐gated Ion Channels. Jie Zheng, University of California at Davis, Davis, California, USA Kimberly Matulef, ...
For example, gating pores in Nav1.5 and Kv7.2 channels may underlie mixed arrhythmias associated with dilated cardiomyopathy ( ... For example, gating pores in Nav1.5 and Kv7.2 channels may underlie mixed arrhythmias associated with dilated cardiomyopathy ( ... or a gating pore.Gating pore currents have recently been shown to cause periodic paralysis phenotypes. There is also increasing ... or a gating pore.Gating pore currents have recently been shown to cause periodic paralysis phenotypes. There is also increasing ...
The fast-acting ligand-gated ion channels (LGICs) constitute a group that encompasses nicotinic ACh, 5-HT3, GABAA and glycine ... Evolutionary history of the ligand-gated ion-channel superfamily of receptors.. Ortells MO1, Lunt GG. ...
... channels. This raises the fundamentally important question: just what makes a Na+ channel conduct Na+ ions? Here we explore ion ... Ion conduction and conformational flexibility of a bacterial voltage-gated sodium channel. Céline Boiteux, Igor Vorobyov, and ... Ion conduction and conformational flexibility of a bacterial voltage-gated sodium channel ... Voltage-gated Na+ channels play an essential role in electrical signaling in the nervous system and are key pharmacological ...
The majority of ion channels fall into two broad categories: voltage-gated ion channels (VGIC) and ligand-gated ion channels ( ... The majority of ion channels fall into two broad categories: voltage-gated ion channels (VGIC) and ligand-gated ion channels ( ... Other Ion Channels. Antibodies to Other Ion Channels. Ion Exchangers and Co-Transporters. Ion Probes. Ionophores. Antibodies to ... the ATP-gated channels, the cyclic nucleotide-gated channels (CNG) and aquaporins (water channels). ...
Ligand-gated ion channel synonyms, Ligand-gated ion channel pronunciation, Ligand-gated ion channel translation, English ... dictionary definition of Ligand-gated ion channel. adj exhibiting an ordering of particles that is a result of the addition of ... acting on voltage-gated ion channels, (2) acting on the ligand-gated ion channel, and (3) acting on other receptors.. ... The glutamate-gated chloride channel (GluCl) is a member of the "Cys-loop" superfamily of ligand-gated ion channels. GluCls ...
Voltage-gated ion channels play fundamental roles in neuronal excitability and therefore dysfunctional channels can cause ... physiology Hydrogen-Ion Concentration Ion Channel Gating/*physiology Magnesium/physiology Membrane Potentials Oocytes/* ... Voltage-gated ion channels regulate the electric activity of excitable tissues, such as the heart and brain. Therefore, ... 2. Lipoelectric modification of ion channel voltage gating by polyunsaturated fatty acids. Open this publication in new window ...
Lets continue with the ion channels, membrane potential and synaptic transmission. 2000+ courses from schools like Stanford ... 6.4 Ion channel, membrane potential and synaptic transmission I15:12. 6.5 Ion channel, membrane potential and synaptic ... 6.6 Ion channel, membrane potential and synaptic transmission III12:53. 6.7 Ion channel, membrane potential and synaptic ... Ion channels, membrane potential and synaptic transmission. Lets continue with the ion channels, membrane potential and ...
The Gene Ontology (GO) project is a collaborative effort to address the need for consistent descriptions of gene products across databases. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated gene data at MGI are provided in Term Detail reports.
Glutamate receptors that function as ligand-gated ion channels are essential components of cell-cell communication in the ... This modular design also suggests an evolutionary link between a ligand-gated ion-channel family and voltage-gated ion channels ... Unraveling the modular design of glutamate-gated ion channels Trends Neurosci. 1995 Apr;18(4):161-8. doi: 10.1016/0166-2236(95) ... Glutamate receptors that function as ligand-gated ion channels are essential components of cell-cell communication in the ...
This webinar will focus on studies of neurotransmitter-activated ion channels as well as GABAA, NMDA, and nicotinic ... Key Ligand-Gated Ion Channels in CNS Drug Discovery. Ion channel structure, function and involvement in disease have been ... Ligand-gated ion channels (i.e., ion-conducting receptors that are activated by endogenous chemical signals such as ... profiling and mechanism-of-action studies in ligand-gated ion channels.. This webinar focuses on studies of neurotransmitter- ...
This key function has two consequences: (i) these receptor channels are major targets for drug discovery because of their ... Ligand-gated ion channels (LGIC) play a central role in inter-cellular communication. ... Ligand-gated ion channels (LGIC) play a central role in inter-cellular communication. This key function has two consequences: ( ... Nasiripourdori A, Taly V, Grutter T, Taly A. From Toxins Targeting Ligand Gated Ion Channels to Therapeutic Molecules. Toxins. ...
Here, we review cnidarian toxins known to target voltage-gated ion channels, the specific channel types targeted, and, where ... Voltage-gated ion channels generate electrical activity in excitable cells. As such, they are essential components of ... known, the sites of action of cnidarian toxins on different channels. ...
  • Sodium channel mutations in humans and animals result in seizures, rare forms of familial migraine headache, movement and pain disorders (Catterall, 2000). (epa.gov)
  • In a joint project with the Department of Molecular Pharmacology at RWTH Aachen University, we are looking for a PhD student to join our research group on ion channels and transporters. (nature.com)
  • The Department of Molecular Pharmacology offers state-of-the-art methods to study ligand-gated ion channels by electrophysiology and molecular biology techniques. (nature.com)
  • Natural gates can be altered and augmented using synthetic chemistry and molecular biology to develop channels with completely new functional properties. (nih.gov)
  • This review covers the molecular principles that guide the engineering of light-gated ion channels for applications in biology and medicine. (nih.gov)
  • We have used multimicrosecond simulations to provide molecular-level descriptions of sodium channel function. (pnas.org)
  • Ion channel structure, function and involvement in disease have been exquisitely detailed by traditional electrophysiological and molecular biological methods. (criver.com)
  • As for other large protein superfamilies, understanding the molecular relationships among family members, developing a unified, rational nomenclature for the ion channel families and subfamilies, and assigning physiological functions and pharmacological significance to each family member has been an important challenge. (aspetjournals.org)
  • The nine articles that follow the overview begin with an introductory section that presents the currently accepted nomenclature for each family of ion channels, describes their molecular relationships, and summarizes the main aspects of their structure and function. (aspetjournals.org)
  • The molecular understanding of ion permeation is thus a central issue in the study of these ion channels. (esrf.eu)
  • However, the molecular mechanisms of ion permeation in pLGICs are complex mechanisms involving protein residues, ions and water molecules that interact together dynamically and transiently as the ions flow down the channel. (esrf.eu)
  • To understand the molecular mechanisms of ion permeation, we solved the crystal structure of GLIC at 2.4 Å, revealing for the first time the hydration geometry in the pore of a pLGIC ( Figure 52b ). (esrf.eu)
  • Despite this, the molecular composition of P2X4 containing ion channels in targets tissues is unclear, though evidence exists for homo- and heteromeric assembly of P2X4 in overexpressed systems. (findaphd.com)
  • Thirdly, collaborators of ours identified new molecular constraints for different states along the gating pathway. (diva-portal.org)
  • Further, simulations of the simple ion channel antiamoebin were performed where different molecular models of the channel were evaluated by calculating ion conduction rates, which were compared to experimentally measured values. (diva-portal.org)
  • The α 1 subunit pore (~190 kDa in molecular mass) is the primary subunit necessary for channel functioning in the HVGCC, and consists of the characteristic four homologous I-IV domains containing six transmembrane α-helices each. (wikipedia.org)
  • In turn, the voltage sensor, a positively charged transmembrane segment called S4, moves towards the outside of the cell through a small molecular gasket called a gating pore. (safein4.com)
  • Because neurons use ion channels to transmit sensory information, light-gated ion channels could restore the senses of those such as the blind who have neural damage. (photonics.com)
  • Using modified potassium channels - dubbed SPARK (synthetic photoisomerizable azobenzene-regulated K+) - they have studied action potential firing of hippocampal neurons. (photonics.com)
  • In photoreceptors and olfactory neurons, CNG channels play an essential role in transducing sensory stimuli into electrical and chemical responses. (els.net)
  • Subunit stoichiometry of CNG channels in photoreceptors and olfactory neurons. (els.net)
  • Although these ion channels are well known to operate stochastically, most computational models of dendritic neurons instead make the approximation that ionic conductances are deterministic. (springer.com)
  • We show how this approximation breaks down for dendritic neurons, with the relative functional influence of stochastic ion channel gating likely to depend strongly on neuron type. (springer.com)
  • An important consequence of stochastic gating of ion channels may be that it causes dendritic neurons to integrate synaptic inputs probabilistically, rather than in the all or nothing fashion predicted by deterministic models. (springer.com)
  • Bittner KC, Andrasfalvy BK, Magee JC (2012) Ion channel gradients in the apical tuft region of CA1 pyramidal neurons. (springer.com)
  • Dorval AD Jr, White JA (2005) Channel noise is essential for perithreshold oscillations in entorhinal stellate neurons. (springer.com)
  • shal is a K+ channel localized to the soma of pyloric neurons (Baro et al. (nih.gov)
  • It has long been recognized that the fast response of neurons to GABA that is blocked by bicuculline and picrotoxin is due to direct activation of an anion channel. (wikipedia.org)
  • The increased chloride conductance drives the membrane potential towards the reversal potential of the Cl¯ ion which is about -75 mV in neurons, inhibiting the firing of new action potentials . (wikipedia.org)
  • Cyclic nucleotides are small ligands used to control the gating of CNG channels. (els.net)
  • A subclass of ion channels that open or close in response to the binding of specific Ligands . (jove.com)
  • In addition, the structural models of GLIC bound to desflurane and propofol at pH 4.0 fail to reveal differences at the level of the pore domain compared with the structure of the channel at the same pH but not bound to these general anesthetics, even when electrophysiological recordings show that the binding of these ligands favors a nonconductive conformation ( 8 ). (pnas.org)
  • In particular, ion channel molecules examined in this study bind to ligands and the central region of the molecules far from the binding site is considered to change greatly. (lightsources.org)
  • One broadly applicable manifestation of this approach are covalently attached photochromic tethered ligands (PTLs) that allow activating ligand-gated ion channels with outstanding spatial and temporal resolution. (ist.ac.at)
  • Our study reveals the first structure of a pLGIC at high resolution and provides an important model system for the investigation of the general mechanisms of ion permeation and gating within the family. (nature.com)
  • Permeation describes the ability of ion channels to selectively determine which ions can move through them. (els.net)
  • The disruption of S4-GCTC interactions allows these crevices to communicate and create a fast activating and non-inactivating alternative cation-selective permeation pathway of low conductance, or a gating pore. (frontiersin.org)
  • Here we explore ion permeation on multimicrosecond timescales using the purpose-built Anton supercomputer. (pnas.org)
  • The crystal structure of GLIC, a prokaryotic homolog of the family was solved in an open form of the channel and provided a significant advance in the possibility to study ion permeation [2-. (esrf.eu)
  • In addition, CNG channels contain a cyclic nucleotide‐binding domain in the C ‐terminus of each subunit, connected to the transmembrane domain by a region called the C‐linker. (els.net)
  • b) Structure of the cytoplasmic domain from a single subunit of HCN2 channels (PDB: 1Q5O). (els.net)
  • The TMD forms a narrow channel lined by the M2 helices from each subunit (grey). (esrf.eu)
  • The movement of four S4s, one from each identical subunit of Shaker, is coupled to the "gate" which opens and closes the pore. (illinois.edu)
  • An alpha subunit, consisting on its own of four repeating trans-membrane domains forming the actual pore, forms the core of the channel and is functional on its own. (axonmedchem.com)
  • Propofol binding to an intra-subunit site of GLIC shifted the tilting angles of TM2 towards closure at the hydrophobic gate region, consistent with propofol inhibition of GLIC. (biochemj.org)
  • Cyclic nucleotide‐gated (CNG) ion channels are activated by cAMP or cGMP, crucial intracellular messenger molecules that regulate a wide variety of physiological activities. (els.net)
  • The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a family of cation channels activated by hyperpolarized membrane potentials and stimulated by intracellular cyclic nucleotides. (scielo.br)
  • We isolate the likely protonation states of the EEEE ring and observe a striking flexibility of the filter that demonstrates the necessity for extended simulations to study conduction in this channel. (pnas.org)
  • We construct free energy maps to reveal complex multi-ion conduction via knock-on and "pass-by" mechanisms, involving concerted ion and glutamate side chain movements. (pnas.org)
  • Evidence exhibits that HCN channels play critical roles in the generation and conduction of the electrical impulse and the physiopathological process of some cardiac diseases. (scielo.br)
  • In the healthy adult heart, HCN channels are predominantly expressed in the conduction system, especially in the sinoatrial node, HCN4 has been determined as the principal HCN isoform in sinoatrial node cells. (scielo.br)
  • Under normal conditions, HCN channels are poorly expressed outside the cardiac pacemaking and conduction system [ 11 , 18 - 20 ] , but it changes during cardiac disease. (scielo.br)
  • In the GLIC structure, the Glu222 carboxylate groups are flexible and continuously exchange between alternative conformations, thus facilitating ion transport. (esrf.eu)
  • The mutated GLIC (GLIC4) became insensitive to the anaesthetics propofol and etomidate, as well as the channel blocker picrotoxin. (biochemj.org)
  • Unlike small-molecule inhibitors, antibodies are highly selective for target antigens but mostly fail to antagonize ion channel functions. (nih.gov)