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

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)

Definition of Voltage-gated channel in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is Voltage-gated channel? Meaning of Voltage-gated channel as a finance term. What does Voltage-gated channel mean in finance?
There are mechanisms, notably ozone degradation, that can damage a single channel of two-channel microarray experiments. Resulting analyses therefore often choose between the unacceptable inclusion of poor quality data or the unpalatable exclusion of some (possibly a lot of) good quality data along with the bad. Two such approaches would be a single channel analysis using some of the data from all of the arrays, and an analysis of all of the data, but only from unaffected arrays. In this paper we examine a combined approach to the analysis of such affected experiments that uses all of the unaffected data. A simulation experiment shows that while a single channel analysis performs relatively well when the majority of arrays are affected, and excluding affected arrays performs relatively well when few arrays are affected (as would be expected in both cases), the combined approach out-performs both. There are benefits to actively estimating the key-parameter of the approach, but whether these compensate
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 ...
2 TMS ( P-loop) Ca2+-gated K+ channel, MthK (see Jiang et al., 2002 for the crystal structure, and Parfenova et al., 2006 for mutations affecting open probability). For the studies of ion permeation and Ca2+ blockage, see Derebe et al., 2011. (structures: 3LDD_A and 2OGU_A.). Voltage-dependent K+ channels including MthK which lacks a canonical voltage sensor can undergo a gating process known as C-type inactivation, which involves entry into a nonconducting state through conformational changes near the channels selectivity filter (Thomson and Rothberg, 2010). C-type inactivation may involve movements of transmembrane voltage sensor domains. In the absence of Ca2+, a single structure in a closed state was observed by cryoEM that was highly flexible with large rocking motions of the gating ring and bending of pore-lining helices (Fan et al. 2020). In Ca2+-bound conditions, several open-inactivated conformations were present with the different channel conformations being distinguished by rocking ...
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 ...
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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.. ...
Most known small-molecule inhibitors of voltage-gated ion channels have poor subtype specificity because they interact with a highly conserved binding site in the central cavity. Using alanine-scanning mutagenesis, electrophysiological recordings and molecular modeling, we have identified a new drug-binding site in Kv1.x channels. We report that Psora-4 can discriminate between related Kv channel subtypes because, in addition to binding the central pore cavity, it binds a second, less conserved site located in side pockets formed by the backsides of S5 and S6, the S4-S5 linker, part of the voltage sensor and the pore helix. Simultaneous drug occupation of both binding sites results in an extremely stable nonconducting state that confers high affinity, cooperativity, use-dependence and selectivity to Psora-4 inhibition of Kv1.x channels. This new mechanism of inhibition represents a molecular basis for the development of a new class of allosteric and selective voltage-gated channel inhibitors.
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, 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 ...
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]. ...
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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.
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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 ...
Mammalian cells are equipped with a large number of ion channels with diverse activation mechanisms and/or modalities. Ion channels are mainly located in the plasma membrane and thus serve crucial molecular mechanisms that transduce extracellular physical, biochemical or biological signals to intracellular events via mediating the movement of ions, particularly Ca2+ entry to elevate the intracellular Ca2+ level. Ion channels are also found in the membrane of intracellular organelles and regulate the ion homeostasis in such intracellular compartments as well as the cytosol. As such, ion channels play an important role in a wide range of physiological processes, which are not restricted to cell excitability. Accumulating evidence show that alterations in the expression and/or function of both the ion-forming or auxiliary subunits occur in neoplastic and malignant cells, markedly influencing cell apoptosis, proliferation, migration and invasion. In addition, ion channels significantly modulate the function
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 ...
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Voltage-dependent ion channels have been found in the plasma membrane of the yeast Saccharomyces cerevisiae. Ion channel activities were recorded from spheroplasts or patches of plasma membrane with the patch-clamp technique. The most prominent activities came from a set of potassium channels with the properties of activation by positive but not negative voltages, high selectivity for potassium over sodium ion, unit conductance of 20 picosiemens, inhibition by tetraethylammonium or barium ions, and bursting kinetics. ...
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, ...
The cell membranes of all organisms contain ion channels that permit ions to pass into or out of the cell, and these channels play extremely important roles in fundamental physiological processes such as heartbeats and the rapid conduction of signals along neurons. An important property of these ion channels is their selective conductivity-they selectively permit the passage of particular ions. For example, potassium channels more readily permit the passage of potassium ions than the passage of sodium ions, despite the fact that potassium ions are larger.
Neural activity depends on the kinetic properties of ion channels expressed in neurons. Small changes in these properties can dramatically affect synaptic integration, membrane excitability and circuit function. Like all biochemical processes, the kinetics of ion channels have an exponential temperature dependence and the exponent (the Q10) differs several-fold between ion channel types within species [1-3]. In warm-blooded animals such as mammals, deviations in temperature of only a few degrees Celsius can thus disrupt neural activity and lead to loss of consciousness or death. However, cold blooded animals, including all invertebrates, manage to survive and function despite temperature fluctuations of tens of degrees Celsius [1]. How is this robustness achieved? One possibility is that the self-regulating, activity-dependent mechanisms that maintain neuronal properties in cold-blooded animals operate in a way that specifically gives rise to temperature robustness. In this work we develop a ...
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Voltage-gated ion channels are present in the excitable cell membranes of heart, skeletal muscle, brain and nerve cells. Blocking or modulating such channels can have a therapeutic effect, or may interfere with normal cell function. As a result, compounds that affect voltage-gated ion channels are important targets in drug discovery.
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 ...
Cobalt 20 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 ...
Cobalt 20 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
CACNB1 (calcium voltage-gated channel auxiliary subunit beta 1), 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.
TY - JOUR. T1 - A conserved glutamate is important for slow inactivation in K+ channels. AU - Larsson, H. Peter. AU - Elinder, Fredrik. N1 - Funding Information: We thank Drs Peter Århem, Peter Löw, Staffan Johansson, and Bo Rydqvist for discussions and suggestions. We are grateful to Stefan Plantman and Kristina Hasslund for some of the recordings and to Carol Larsson and Russell Hill for editing the manuscript. This work was supported by grants from the Swedish Medical Research Council (F. E. and P. L.)Åke Wibergs stiftelse (F. E. and P. L.), Magn. Bergvalls Stiftelse (F. E. and P. L.), the Swedish Society of Medicine (P. L.), and Jeanssons Stiftelser (P. L.). F. E. and P. L. have junior research positions at the Swedish Medical Research Council. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 2000. Y1 - 2000. N2 - Voltage-gated ion channels undergo slow inactivation during prolonged depolarizations. We investigated the role of a conserved glutamate at the extracellular ...
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 ...
Sumoylation has recently been recognized as an important mechanism of cellular activity but until now its 60-or-so known targets were primarily nuclear proteins, mostly involved in gene transcription. The findings expand the influence of SUMO-related activity in biology, Goldstein said, a great and exciting surprise. There is still a good deal that we dont understand about this system, he said, but now we know where to look and why we must go there. SUMO may very well act on other ion channels that have yet to reveal their function because they were silent like K2P1 ...
January 8, 2018. Subtype-selective modulation of ion channels is often important, but extremely difficult to achieve for drug development. Using Nav1.7 as an example, we show that this challenge could be attributed to poor design in ion channel assays, which fail to detect most potent and selective compounds and are biased toward nonselective mechanisms. By exploiting different drug binding sites and modes of channel gating, we successfully direct a membrane potential assay toward non-pore-blocking mechanisms and identify Nav1.7-selective compounds. Our mechanistic approach to assay design addresses a significant hurdle in Nav1.7 drug discovery and is applicable to many other ion channels. ...
Voltage-activated K+ channels are integral membrane proteins that open or close a K(+)-selective pore in response to changes in transmembrane voltage. Although the S4 region of these channels has been implicated as the voltage sensor, little is known about how opening and closing of the pore is acco …
Akerfeldt, Karin S., et al. Synthetic peptides as models for ion channel proteins. Accounts of chemical research 26.4 (1993): 191-197.. ...
As ion channels influence many aspects of biology, artificially light-responsive ion channels can facilitate experimental manipulation, allowing neuro
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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 ...
Ligand-gated ion channel. *Purinergic receptor. Enzyme-linked receptor. *Serine/threonine-specific protein kinase ...
Kienker, P. (1989-04-22). "Equivalence of Aggregated Markov Models of Ion-Channel Gating". Proceedings of the Royal Society B: ... Goychuk, Igor; Hänggi, Peter (2004-11-24). "Fractional diffusion modeling of ion channel gating". Physical Review E. 70 (5): ... "Using independent open-to-closed transitions to simplify aggregated Markov models of ion channel gating kinetics". Proceedings ... Colquhoun, D.; Hawkes, A. G. (1982-12-24). "On the Stochastic Properties of Bursts of Single Ion Channel Openings and of ...
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 ...
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 ...
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 ...
Catterall, William (2007). "Voltage-gated ion channels and gating modifier toxins". Toxicon. 49 (2): 124-41. doi:10.1016/j. ... that inhibits fast inactivation of voltage gated sodium-channels (VGSCs). The LmαTX3 toxin derives the first part of its name ... Site 3 toxins prevent a component of outward gating charge movement associated with channel inactivation, it is likely that ... Bosmans, Frank (2007). "Voltage-gated sodium channel modulation by scorpion α-toxins". Toxicon. 49 (2): 142-158. doi:10.1016/j. ...
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. ...
Banghart, M. R.; Volgraf, M.; Trauner, D. (December 2006). "Engineering light-gated ion channels". Biochemistry. 45 (51): 15129 ...
Kaupp UB, Seifert R (July 2002). "Cyclic nucleotide-gated ion channels". Physiol. Rev. 82 (3): 769-824. CiteSeerX ... Increases in concentration of the second messenger cAMP may lead to the activation of cyclic nucleotide-gated ion channels ... "A β2 adrenergic receptor signaling complex assembled with the Ca2+ channel Cav1.2". Science. 293 (5527): 98-101. doi:10.1126/ ...
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. CiteSeerX ... 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 ...
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 ...
Yin J, Kuang Z, Mahankali U, Beck TL (November 2004). "Ion transit pathways and gating in ClC chloride channels". Proteins. 57 ... Like all ClC channels, ClC-5 needs to dimerize to create the pore through which the ions pass. ClC-5 can form both homo- and ... Lamb FS, Clayton GH, Liu BX, Smith RL, Barna TJ, Schutte BC (March 1999). "Expression of CLCN voltage-gated chloride channel ... Lamb FS, Clayton GH, Liu BX, Smith RL, Barna TJ, Schutte BC (March 1999). "Expression of CLCN voltage-gated chloride channel ...
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 ...
"Voltage-gated ion channels and gating modifier toxins" (PDF). 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 ...
Catterall WA, Cestèle S, Yarov-Yarovoy V, Yu FH, Konoki K, Scheuer T (February 2007). "Voltage-gated ion channels and gating ... 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 ...
"Insect olfactory receptors are heteromeric ligand-gated ion channels". Nature. 452 (7190): 1002-6. doi:10.1038/nature06850. ... "Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels". Nature. 452 (7190): 1007- ...
Kienker, P. (1989). "Equivalence of Aggregated Markov Models of Ion-Channel Gating". Proceedings of the Royal Society B: ... Since the ion channel is either opened or closed, when recording the number of ions that go through the channel when time ... "Using independent open-to-closed transitions to simplify aggregated Markov models of ion channel gating kinetics". Proceedings ... Colquhoun, D.; Hawkes, A. G. (1982). "On the Stochastic Properties of Bursts of Single Ion Channel Openings and of Clusters of ...
Catterall WA, Cestèle S, Yarov-Yarovoy V, Yu FH, Konoki K, Scheuer T (February 2007). "Voltage-gated ion channels and gating ... Cn2 specifically targets the mammalian voltage-gated sodium channel (VGSC) Nav1.6. It is likely that Cn2 binds most strongly to ... The toxin specifically targets mammalian Nav1.6 voltage-gated sodium channels (VGSC). Cn2 is a neurotoxin named after and ... Scorpion toxins affecting the gating mechanisms of sodium channels are classically divided in two major classes: α- and β- ...
Catterall WA, Cestèle S, Yarov-Yarovoy V, Yu FH, Konoki K, Scheuer T (February 2007). "Voltage-gated ion channels and gating ... Cll2 targets voltage-gated sodium channels (VGSCs). It specifically binds to and alters the Nav1.6 channel, as well as, but to ... It affects voltage-dependent activation, conductance and resurgent currents of voltage gated sodium channels by binding to site ... Cll1, on the other hand, influences the channels Nav 1.1 to Nav 1.6 all in an equal way. The LD50 for Cll is 3.30 mg/kg. The ...
See also lipid-gated ion channels. The first three roles are not mutually exclusive. For example, PA may be involved in vesicle ... Phosphatidic acids are anionic phospholipids important to cell signaling and direct activation of lipid-gated ion channels. ... PA plays very important role in phototransduction in Drosophila PA is a lipid ligand that gates ion channels. ... Robinson, CV; Rohacs, T; Hansen, SB (September 2019). "Tools for Understanding Nanoscale Lipid Regulation of Ion Channels". ...
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 ...
Hansen, SB (May 2015). "Lipid agonism: The PIP2 paradigm of ligand-gated ion channels". Biochimica et Biophysica Acta (BBA) - ... PIP2's interaction with many ion channels suggest that the intact form of PIP2 has an important signaling role independent of ... PIP2 binds directly to ion channels and modulates their activity. PIP2 was shown to directly agonizes Inward rectifying ... As a second messenger, it is recognized by the inositol triphosphate receptor (IP3R), a Ca2+ channel in the endoplasmic ...
Hansen, SB (May 2015). "Lipid agonism: The PIP2 paradigm of ligand-gated ion channels". Biochimica et Biophysica Acta (BBA) - ... ion channel conductance, endocrine function and neurotransmission. All family members are capable of catalyzing the hydrolysis ... which becomes activated in conjunction with binding calcium ions. This results in a host of cellular responses through ... most notably PIP2 dependent channels and transporters responsible for setting the cell's membrane potential. The hydrolytic ...
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 ...
inhibitory extracellular ligand-gated ion channel activity. • GABA-gated chloride ion channel activity. • transmitter-gated ion ... ion channel activity. • benzodiazepine receptor activity. • chloride channel activity. • extracellular ligand-gated ion channel ... which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as ... ion transport. • regulation of response to drug. • central nervous system development. • chloride transport. • ion ...
Dual-gate field-effect transistors have a single channel with two gates in cascode, a configuration optimized for high- ... Nanofluidic transistor, controls the movement of ions through sub-microscopic, water-filled channels.[87] ... and a gate potential can "enhance" the conduction. For the depletion mode, the channel is on at zero bias, and a gate potential ... the gate), oxide (the insulation), and semiconductor. Unlike IGFETs, the JFET gate forms a p-n diode with the channel which ...
... resulting in the closure of cyclic nucleotide-gated Na+ ion channels located in the photoreceptor outer segment membrane. ... which opens ion channels (largely sodium channels, though calcium can enter through these channels as well). The positive ... Reduction in cGMP allows the ion channels to close, preventing the influx of positive ions, hyperpolarizing the cell, and ... Unstimulated (in the dark), cyclic-nucleotide gated channels in the outer segment are open because cyclic GMP (cGMP) is bound ...
"A Practical and Efficient Synthesis of the Selective Neuronal Acetylcholine-Gated Ion Channel Agonist (S)-(−)-5-Ethynyl-3-(1- ...
ABC · CBS · NBC · PBS · FOX · MyNetworkTV · CNBC · USA Network · Ion · Nickelodeon · E! · CBC · Cartoon Network ... 13th Street Universal · Diva Universal · KidsCo[nu 5] · Movies 24 · Steel[nu 6] · Studio Universal · Syfy · Universal Channel ... Golf Channel · NBC Sports Network · Universal Sports (bagian pemilik)[nu 4] · Alli ... "America's Fastest Growing News Channel"[2]. "A Fuller Spectrum of News"[3]. "Lean Forward"[4]. ...
These fibres send information by stretch-sensitive mechanically-gated ion-channels of the axons.[3] ... This opens stretch-sensitive ion channels of the sensory endings, leading to an influx of sodium ions. This raises the resting ...
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 ...
See also: Receptor/signaling modulators • Ion channel modulators. Taxon identifiers. *Wikidata: Q35625 ... the journey begins when farmers sell a portion of their produce to village traders who collect produce right at the farm gate.[ ... States in which ginger is exported follow the marketing channels of vegetable marketing in India, and the steps are similar to ... water channels are made 60-80 ft apart to irrigate the crop.[29] ...
calcium channel activity. • metal ion binding. • voltage-gated ion channel activity. • ion channel activity. • protein binding ... high voltage-gated calcium channel activity. • voltage-gated calcium channel activity involved in AV node cell action potential ... voltage-gated calcium channel activity. • voltage-gated calcium channel activity involved in cardiac muscle cell action ... calcium ion transmembrane transport via high voltage-gated calcium channel. • membrane depolarization during AV node cell ...
Research in lithium-ion batteries. *Silicon-air battery. *Thermal energy storage. *Ultracapacitor ... Quantum logic gates. *Quantum machine. *Quantum machine learning. *Quantum metamaterial. *Quantum metrology ...
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 Weather Channel's Special Report: Vulnerable Cities - New Orleans, Louisiana". Archived from the original on April 27, 2006 ... the congregation consecrated a new synagogue on land purchased from the Reform Congregation Gates of Prayer in Metairie.[116] ... 49 WPXL (Ion). *54 WUPL (MyNetworkTV). WWOZ,[199] the New Orleans Jazz and Heritage Station, broadcasts[200] modern and ... "Discovery Channel. Archived from the original on June 14, 2006. Retrieved June 17, 2006.. ...
Quantum channel *Quantum network. *Quantum cryptography *Quantum key distribution. *Quantum energy teleportation ...
... also has a small blocking effect on hERG channels without alteration of the gating kinetics.[4] ... By blocking specifically the Kv4 channels, AmmTX3 reduces the A-type potassium current through these channels almost completely ... "Kv4 channels underlie A-currents with highly variable inactivation time courses but homogeneous other gating properties in the ... The toxin is known for its ability to act as a specific Kv4 channel blocker, and thereby reducing the A-type potassium current ...
Because the 20S particle's central channel is narrow and gated by the N-terminal tails of the α ring subunits, the substrates ... cells expressing these proteasomes show enhanced resistance to toxicity induced by metallic ions such as cadmium.[23][25] ... "The axial channel of the proteasome core particle is gated by the Rpt2 ATPase and controls both substrate entry and product ... The mechanism by which the proteasomal ATPase open this gate has been recently elucidated.[18] 20S gate opening, and thus ...
WDM channels (per core) Per channel speed Distance 2018 Hao Hu, et al. (DTU, Fujikura & NTT)[39] 768 Tbit/s. (661 Tbit/s) ... Research in lithium-ion batteries. *Silicon-air battery. *Thermal energy storage. *Ultracapacitor ... per fiber is the per-channel data rate reduced by the FEC overhead, multiplied by the number of channels (usually up to eighty ... is the practice of multiplying the available capacity of optical fibers through use of parallel channels, each channel on a ...
The membrane can then be analyzed on a patch clamp apparatus to determine the phenotype of the ion channels embedded in it. It ... I. Identification and functional characterization of KvLm, a voltage-gated K+ channel from Listeria monocytogenes. Journal of ... Specially prepared giant spheroplasts of Gram-negative bacteria can be used to study the function of bacterial ion channels ... Martinac, B., Buechner, M., Delcour, A. H., Adler, J., and Kung, C. (1987) Pressure-sensitive ion channel in Escherichia coli. ...
H. Guan, X. Wang, H. Li, C. Zhi, T. Zhai, Y. Bando and D. Golberg : «CoO octahedral nanocages for high-performance lithium ion ... Z. Xu, C. Zhang, W. Wang, Y. Bando, X. Bai, D. Golberg : «Lateral piezopotential-gated field-effect transistor of ZnO nanowires ... Melting of metallic electrodes and their flowing through a carbon nanotube channel within a device» Adv. Mater. 25 (2013) 2693- ... E.A. Obraztsova, D.V. Shtansky, A.N. Sheveyko, M. Yamaguchi, A.M. Kovalskii and D. Golberg : «Metal ion implantation of ...
transmitter-gated ion channel activity. • chloride channel activity. • extracellular ligand-gated ion channel activity. • ... extracellular-glycine-gated chloride channel activity. • ion channel activity. • transmembrane signaling receptor activity. ... chloride channel complex. • cell junction. • dendrite. • glycinergic synapse. • integral component of postsynaptic ... ion transport. • synaptic transmission, glycinergic. • chloride transport. • neuropeptide signaling pathway. • chloride ...
Ion channel blockers. *Anticonvulsants (e.g., gabapentin, pregabalin, carbamazepine, oxcarbazepine, lacosamide, lamotrigine) ... These studies suggested that lamotrigine acts presynaptically on voltage-gated sodium channels to decrease glutamate release. ... but could relate to actions of the drug on voltage-activated calcium channels. Lamotrigine blocks T-type calcium channels ... Lamotrigine is a member of the sodium channel blocking class of antiepileptic drugs.[60] This may suppress the release of ...
... the voltage-gated potassium channel KCNH2 gene (hERG/Kv11.1), and the α1D-adrenoceptor ADRA1D gene.[58] ... The cause is thought to be blockade of hERG voltage-gated potassium channels.[41][42] The risks are dose-dependent, and appear ... 5-HT3 serotonin ion. channel antagonists. *Alosetron. *Azasetron. *Bemesetron. *Cilansetron. *Clozapine ...
GABA acts via binding to its receptors which include the ligand gated ion channels, GABAA and GABAC and the G-protein couple ... the release through presynaptic effects through a voltage dependent inhibition of high voltage activation of calcium channels. ... restoration of GABAergic synaptic activity and region-specific restoration of GABAA receptor associated chloride channel ...
The development of higher rated insulated-gate bipolar transistors (IGBTs), gate turn-off thyristors (GTOs) and integrated gate ... Corona discharge is the creation of ions in a fluid (such as air) by the presence of a strong electric field. Electrons are ... For an 8 GW 40 km link laid under the English Channel, the following are approximate primary equipment costs for a 2000 MW 500 ... integrated gate-commutated thyristors (IGCTs), MOS-controlled thyristors (MCTs) and insulated-gate bipolar transistors (IGBT).[ ...
ligand-gated ion channel activity. • potassium channel regulator activity. • cadherin binding. • Ras guanyl-nucleotide exchange ... regulation of potassium ion import. • regulation of voltage-gated potassium channel activity involved in ventricular cardiac ... ion channel binding. • cytoskeletal protein binding. • protein C-terminus binding. • ionotropic glutamate receptor binding. • ... regulation of potassium ion export across plasma membrane. • MAPK cascade. • cell-cell adhesion. • maintenance of postsynaptic ...
Ion channel blockers. *Anticonvulsants (e.g., gabapentin, pregabalin, carbamazepine, oxcarbazepine, lacosamide, lamotrigine) ... including suppression of voltage-gated Ca2+ currents and activation of G protein-coupled receptor-operated K+ currents). ... and sodium channels in the cardiac muscle, leading to decreased cardiac conduction and cardiotoxicity. Selectivity of ...
Binds to the α2δ-1 subunit of voltage gated calcium ion channels in the spinal cord. May also modulate NMDA receptors and ... 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 ...
... resulting in the closing of Na+ cyclic nucleotide-gated ion channels (CNGs). Thus the cell is hyperpolarised. The amount of ... It is believed that the connection strength between cells is caused by the number and types of ion channels embedded in the ... Inside the cell the normal levels of cyclic guanosine monophosphate (cGMP) keep the Na+ channel open, and thus in the resting ... and the accompanying glial cells have been shown to act as fibre-optic channels to transport photons directly to the ...
While the opening and closing of the ion channel is primarily gated by ligand binding, the current flow through the ion channel ... The N-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in ... Activation and opening of the receptor channel thus allows the flow of K+, Na+ and Ca2+ ions, and the influx of Ca2+ triggers ... The NMDA receptor is a glutamate and ion channel protein receptor that is activated when glycine and glutamate bind to it.[2] ...
GluCls are invertebrate-specific members of the Cys-loop family of ligand-gated ion channels present in neurons and myocytes. ... The drug binds to glutamate-gated chloride channels (GluCls) in the membranes of invertebrate nerve and muscle cells, causing ... Yates DM, Wolstenholme AJ (August 2004). "An ivermectin-sensitive glutamate-gated chloride channel subunit from Dirofilaria ... These drugs include statins, HIV protease inhibitors, many calcium channel blockers, lidocaine, the benzodiazepines, and ...
... voltage-gated ion channels directionally propagate electrical signals. Voltage-gated ion-channels are usually ion-specific, and ... IUPHAR-DB Voltage-gated ion channel subunits The IUPHAR Compendium of Voltage-gated Ion Channels 2005 Voltage-Dependent+Anion+ ... 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 ...
Lipid-gated ion channels are a class of ion channels whose conductance of ions through the membrane depends directly on lipids ... PIP2 is a cell membrane lipid, and its role in gating ion channels represents a novel role for the molecule. Kir channels: PIP2 ... Other classes of lipid-gated channels include the mechanosensitive ion channels that respond to lipid tension, thickness, and ... TRP channels: TRP channels were perhaps the first class of channels recognized as lipid-gated. PIP2 regulates the conductance ...
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 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 ...
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, ...
Clinically Approved Ion Channel Inhibitors Close Gates for Hepatitis C Virus and Open Doors for Drug Repurposing in Infectious ...
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 ...
... allowing ions to permeate. Voltage-gated ion channels can either be inacti … ... Voltage-gated ion channels are key molecules for the generation of electrical signals in cells. They are integral membrane ... allowing ions to permeate. Voltage-gated ion channels can either be inactivated from this open state by an additional ... Structure and function of voltage-gated ion channels Naturwissenschaften. 1998 Sep;85(9):437-44. doi: 10.1007/s001140050527. ...
voltage gated ion channel activity, voltage-dependent ion channel activity View GO Annotations in other species in AmiGO ... Enables the transmembrane transfer of an ion by a voltage-gated channel. An ion is an atom or group of atoms carrying an ... Gene Ontology Term: voltage-gated ion channel activity. GO ID. GO:0005244 Aspect. Molecular Function. Description. ... A voltage-gated channel is a channel whose open state is dependent on the voltage across the membrane in which it is embedded. ...
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 ...
This authoritative and comprehensive volume presents a perspective in the molecular and cellular diversity of membrane ion ... Voltage-Gated K+ Channel Genes, K.G. Chandy and G.A. Gutman. Voltage-Gated Sodium Channels, A.L. Goldin. Voltage-Gated Calcium ... Handbook of Receptors and Channels Ligand and Voltage Gated Ion Edited By R. Alan North. ... Handbook of Receptors and Channels: Ligand and Voltage Gated Ion. ISBN , Quantity: ...
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). ...
An unusual mechanism of ion channel regulation generates voltage-dependent gating in the absence of a canonical voltage-sensing ...
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.
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. ...
Ionotropic glutamate receptors form the ion channel pore that activates when glutamate binds to the receptor. There are also ... Antibodies to Ion Channels > Antibodies to Ligand-Gated Ion Channels > Antibodies to Glutamate Receptors ... Ionotropic glutamate receptors form the ion channel pore that activates when glutamate binds to the receptor. There are also ...
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 ...
We further focus on the mechanisms of FFA modulation operating on voltage-gated and ligand-gated ion channel function, ... We further focus on the mechanisms of FFA modulation operating on voltage-gated and ligand-gated ion channel function, ... has been interpreted as a protective mechanism possibly operative on ion channels, which in some cases is of stimulatory nature ... has been interpreted as a protective mechanism possibly operative on ion channels, which in some cases is of stimulatory nature ...
  • In the frame of a research project funded by the German Research Foundation (DFG, , the PhD project will focus on ion permeation, functional mechanisms of ligand activation and subtype-specific ligand interactions in P2X receptors. (
  • Our joint research group uses a combination of molecular biology, electrophysiological experiments and molecular simulations to investigate the structure-dynamics-function relationships of ion channels and receptors and to understand how they can be targeted by drugs. (
  • Based on ion selectivity, functional similarities, and structural homology, this superfamily can be divided into five main types: proteins lacking a PD, voltage gated sodium and calcium channels (Na v , Ca v ), voltage gated potassium channels (K v ), cyclic nucleotide gated channels (CNG), and transient receptors potential channels (TRPs). (
  • Evolutionary history of the ligand-gated ion-channel superfamily of receptors. (
  • The fast-acting ligand-gated ion channels (LGICs) constitute a group that encompasses nicotinic ACh, 5-HT3, GABAA and glycine receptors. (
  • Other, smaller categories exist, such as the vanilloid (TRP) receptors, the ATP-gated channels, the cyclic nucleotide-gated channels (CNG) and aquaporins (water channels). (
  • According to its different targets acting on the organism, the conotoxins can be divided into three categories [3]: (1) acting on voltage-gated ion channels, (2) acting on the ligand-gated ion channel , and (3) acting on other receptors. (
  • All of these nAChRs belong to a family of receptors that are collectively called ligand-gated ion channel receptors. (
  • Our targets in this endeavor, nicotinic acetylcholine receptors and related ligand-gated ion channels , are widely distributed throughout the periphery, autonomic ganglia, and neuromuscular junction. (
  • Nicotine initiates its action by competitively binding at the nicotinic acetylcholine receptors (nAChRs), ligand-gated ion channels on the cell membrane. (
  • The cys-loop family of ligand-gated ion channels (LGICs) consists of the nicotinic acetylcholine, serotonin type-3 (5-HT3), glycine, and GAB[A.sub.A] receptors and is responsible for mediating rapid neurotransmission in the CNS and PNS. (
  • However, as therapeutic targets, ion channels have lagged behind other classes, such as enzymes and G protein-coupled receptors, due primarily to a lack of high-throughput technology adaptable to modern screening methods. (
  • Ligand-gated ion channels (i.e., ion-conducting receptors that are activated by endogenous chemical signals such as neurotransmitters) are particularly challenging targets due to multiple subunit composition and complex modulatory mechanisms. (
  • This webinar focuses on studies of neurotransmitter-activated ion channels as well as GABAA, NMDA, and nicotinic acetylcholine receptors, in that they are validated therapeutic targets in several neurological disorders. (
  • Ionotropic glutamate receptors form the ion channel pore that activates when glutamate binds to the receptor. (
  • In this paper we report two different methodologies for labeling ligand-gated receptors. (
  • Cysteine Loop Ligand-Gated Ion Channel Receptors" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (
  • A subfamily of ligand-gated ion channel receptors that share a characteristic loop which is formed by a disulfide bond between two CYSTEINE residues. (
  • This graph shows the total number of publications written about "Cysteine Loop Ligand-Gated Ion Channel Receptors" by people in Harvard Catalyst Profiles by year, and whether "Cysteine Loop Ligand-Gated Ion Channel Receptors" was a major or minor topic of these publication. (
  • Below are the most recent publications written about "Cysteine Loop Ligand-Gated Ion Channel Receptors" by people in Profiles. (
  • Receptors from the superfamily of pentameric ligand-gated ion channels including gamma aminobutyric acid type A (GABA A ), glycine, 5HT 3 , and neuronal nicotinic acetylcholine receptors are modulated by anesthetics in concentrations that are used clinically. (
  • Pentameric ligand-gated ion channels from the superfamily containing gamma aminobutyric acid type A (GABA A ), glycine, 5HT 3 , and neuronal nicotinic acetylcholine (nACh) receptors are allosterically modulated by clinical concentrations of anesthetics and are thus attractive candidates as mediators of anesthetic action. (
  • The voltage-gated ion channels and their structural relatives comprise a superfamily encoded by at least 143 genes in the human genome and are therefore one of the largest superfamilies of signal transduction proteins, following the G protein-coupled receptors and the protein kinases in number. (
  • Pentameric ligand-gated ion channels (pLGICs) are a major family of membrane receptors that mediate fast chemical transmission of nerve signals in the central and peripheral nervous system [1] . (
  • P2X receptors are trimeric ATP-activated ion channels permeable to Na+, K+ and Ca2+. (
  • Site-directed mutations to specific amino acids within or flanking the M2 transmembrane segments of the anion-selective glycine, GABA(A) and GABA(C) receptors and the cation-selective nicotinic acetylcholine and serotonin (type 3) receptors have revealed discrete, equivalent regions within the ion channel that form the principal selectivity filter, leading to plausible molecular mechanisms and mathematical models to describe how ions preferentially permeate these channels. (
  • Recent physiological, genetic, and biochemical studies have pin-pointed molecular targets for anesthetics and EtOH in the brain as ligand-gated ion channel (LGIC) membrane proteins, especially the pentameric (5 subunit) Cys-loop superfamily of neurotransmitter receptors including nicotinic acetylcholine (nAChRs), GABA(A) (GABA(A)Rs), and glycine receptors (GlyRs). (
  • P2X receptors are ligand-gated ion channels activated by extracellular ATP. (
  • Ligand gated sodium channels (e.g. nicotinic receptors ) are activated by endogenous acetylcholine. (
  • Inotropic glutamate receptors are receptors that pass ions and are named for the? (
  • These results indicate the existence of different gating mechanisms for AMPA and kainate receptors. (
  • Ionotropic glutamate receptors are ligand-gated ion channels that mediate most of the transfer of excitatory information in the brain. (
  • Therefore, it might be expected that these receptors would rely on a common gating mechanism in which similar conformational changes of the agonist-binding domain must operate channel opening and closing. (
  • Indeed, from the analysis of the numerous GluR6 receptor mutants, it appears that residues S689 and A721 in the S2 segment play a significant role in defining the gating properties of kainate receptors (Swanson et al. (
  • Neurotransmitters play key roles in the complex mechanisms of the central nervous system and interact with e.g. ligand-gated ion channel receptors. (
  • Gamma-aminobutyric acid (GABA) has 2 types of receptors, A and B. When GABA binds to a GABA-A receptor, the passage of chloride, a negatively charged ion, into the cell is facilitated via chloride channels (see the image below). (
  • These proteins are structurally related receptor/CI- channel complexes, and are the predominant inhibitory neurotransmitter receptors in the central nervous system. (
  • These neurotransmitters include acetyl-choline, g-aminobutyric acid (GABA), glycine, glutamate, and serotonin (5-hydroxytryptophan), and the ion channels are more commonly referred to as receptors. (
  • Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. (
  • The membrane potential alters the conformation of the channel proteins, regulating their opening and closing. (
  • The conformational change distorts the shape of the channel proteins sufficiently such that the cavity, or channel, opens to allow influx or efflux to occur across the membrane. (
  • The family codes for a structurally conserved scaffold of channel proteins that open in response to the binding of neurotransmitter molecules. (
  • All proteins share a pentameric organization of identical or related subunits that consist of an extracellular ligand-binding domain followed by a transmembrane channel domain. (
  • The exquisite regulation of different CNG channels by divalent cations, calmodulin, phosphorylation and phospholipids allows these proteins to carry out disparate physiological functions with high precision. (
  • Ion channels are membrane proteins that allow ions to diffuse across cellular membranes in a regulated manner. (
  • Voltage sensor domains (VSDs) are a feature of voltage gated ion channels (VGICs) and voltage sensitive proteins. (
  • They are integral membrane proteins which are activated by a depolarized membrane potential resulting in a conformational change, allowing ions to permeate. (
  • Following the first successful cloning of voltage-gated ion channels in 1984 the combination of molecular biological and electrophysiological techniques has been very fruitful in the investigation of the structure and function of these membrane proteins. (
  • One of the main goals of direct structural approaches as applied to ion channels is to determine what these proteins look like in their different functional states. (
  • The editors and contributors to this revised and updated version of the ion channel compendium hope that the unified nomenclatures for the ion channel families presented here will enhance and clarify communication among the many scientists in a broad range of disciplines who work on the ion channel proteins and will provide a valuable reference resource for the ion channel community. (
  • pLGICs are dynamic proteins that couple neurotransmitter binding in their extracellular-domain (ECD) to the opening of ion channels embedded in their transmembrane domain (TMD). (
  • Amino acid residues necessary for pharmacologically relevant allosteric modulation of LGIC function by anesthetics and EtOH have been identified in these channel proteins. (
  • Ion channels are specialized proteins embedded in the membrane. (
  • The ubiquitous inositol 1,4,5-trisphosphate (InsP 3 ) receptor (InsP 3 R) Ca 2+ release channel plays a central role in the generation and modulation of intracellular Ca 2+ signals, and is intricately regulated by multiple mechanisms including cytoplasmic ligand (InsP 3 , free Ca 2+ , free ATP 4− ) binding, posttranslational modifications, and interactions with cytoplasmic and endoplasmic reticulum (ER) luminal proteins. (
  • Voltage gated channel proteins cooperate in the transmission of membrane potentials between nerve cells. (
  • With the recent progress in atomic-scaled biological chemistry it has now become established that these channel proteins provide highly correlated atomic environments that may maintain electronic coherences even at warm temperatures. (
  • We show that, depending on the surrounding carbonyl derived potentials, alkali ions can become highly delocalized in the filter region of proteins at warm temperatures. (
  • We provide estimations about the temporal evolution of the kinetic energy of ions depending on their interaction with other ions, their location within the oxygen cage of the proteins filter region and depending on different oscillation frequencies of the surrounding carbonyl groups. (
  • Ion transport across the relatively impermeable lipid bilayer of the cell membrane is accomplished via membrane proteins known as ion channels, pumps and transporters. (
  • Ethanol alters nerve signalling by interacting with proteins in the central nervous system, particularly pentameric ligand-gated ion channels. (
  • Neurotransmitter ligand-gated ion channels are transmembrane receptor-ion channel complexes that open transiently upon binding of specific ligands, allowing rapid transmission of signals at chemical synapses [ PMID: 1721053 , PMID: 1846404 ]. (
  • Glycine receptor, an inhibitory chloride ion channel composed of alpha and beta subunits [ PMID: 15383648 ]. (
  • Glutamate receptor, an excitatory cation channel of which at least three types have been described (kainate, N-methyl-D-aspartate (NMDA) and quisqualate) [ PMID: 15165736 ]. (
  • Molecular structure and function of the glycine receptor chloride channel. (
  • Structure and gating of the glutamate receptor ion channel. (
  • Ion channels that have been made light sensitive to study their properties include the nicotinic acetylcholine receptor (nAChR), gramicidin A, a voltage-gated potassium channel and - most recently - α-hemolysin. (
  • Over the last few decades, several channels have been successfully rendered responsive to light, including the nicotinic acetylcholine receptor, gramicidin A, a voltage-gated potassium channel, an ionotropic glutamate receptor, alpha-hemolysin, and a mechanosensitive channel. (
  • A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family. (
  • Expression of TRPM8 receptor on presynaptic Ca2+ stores, a novel localization for this ligand-gated ion channel , is also strongly suggested. (
  • Overall, our findings bring to light the limited power of functional studies in intact membranes when it comes to inferring the functional state of a channel in a crystal, at least in the case of the nicotinic-receptor superfamily. (
  • Thus far, in the case of the bacterial members of the nicotinic-receptor superfamily, the use of ligands to select the crystallized conformation of the channel has yielded results that are difficult to interpret. (
  • In this review we summarize data from numerous PUFAs on voltage-gated ion channels containing one or several voltage-sensor domains, such as voltage-gated sodium (NaV), potassium (KV), calcium (CaV), and proton (HV) channels, as well as calcium-activated potassium (KCa), and transient receptor potential (TRP) channels. (
  • The Transient Receptor Potential Vanilloid 2 (TRPV2) channel is a member of the temperature-sensing thermoTRPV family. (
  • Two prokaryotic members of this receptor superfamily family have recently been cloned, one from the cyanobacterium Gloeobacter violaceus ( 2 ) (denoted GLIC) and a homologous channel from the enterobacterium Erwinia chrysanthemi ( 3 ) (denoted ELIC). (
  • Specifically, we consider mutations in the channel pore of nicotinic acetylcholine receptor (nAChR) and the ligand binding domain of a cyclic nucleotide-gated (CNG) ion channel, demonstrating how each mutation can be characterized as only affecting a subset of the biophysical parameters. (
  • This project is highly suited to a student with an interest in ion channel/receptor background in pharmacology and biochemistry. (
  • Here, we dissect the importance of essential prolines in the bacterial receptor Gloeobacter violaceus ligand-gated ion channel (GLIC), an important functional model for the eukaryotic Cys-loop receptor class of ligand-gated ion channels. (
  • If these gating motions are conserved throughout the family, a detailed understanding of the process holds promise for the development of strategies to tune receptor activity. (
  • Activation causes a conformational change of the receptor, leading to the opening of the internal pore, and enabling extra-cellular sodium ions to flow into the cell. (
  • Which of the 4 transmembrane domains in the cys-loop receptor is responsible for forming the ion poor? (
  • 2. They affect how quickly and what types of ions can pass through the receptor. (
  • This receptor functions as a ligand-gated ion channel and may transduce ATP-evoked nociceptor activation. (
  • P2RX3 has several biochemical functions, for example, ATP binding, extracellular ATP-gated cation channel activity, purinergic nucleotide receptor activity. (
  • Thus, these results show the existence of a specific kainate receptor gating mechanism that requires external Na + to be operative. (
  • The structure of these receptor channels is also similar, and not only is there significant homology at the amino acid level, but also the residues within the segments lining the receptor channel impose similar biophysical properties. (
  • The goal is to obtain detailed understanding of ligand-gated ion channel receptor structure and function, which is essential for providing a rational basis for design of therapeutic strategies for treating diseases and disorders within the central nervous system. (
  • The diversity of toxin action on these channels is illustrated by sodium channels, which are the molecular targets for toxins that act at six or more distinct receptor sites on the channel protein. (
  • In contrast, polypeptide toxins alter channel gating by voltage-sensor trapping through binding to extracellular receptor sites, and this toxin interaction has now been modeled at the atomic level for a β-scorpion toxin. (
  • We will test the hypothesis that PTX acts deep in the channel of the homomeric glycine and the heteromeric GABAA receptor. (
  • Recent work from our lab indicates these neurotoxins also block the 5HT3 receptor, a cation-selective ligand-gated ion channel. (
  • and 4) that neurotoxins block the cation-selective 5HT3 receptor through a domain similar to that of the anion- selective channels. (
  • The light-gated glutamate receptor (LiGluR), which consists of the PTL-functionalized GluK2 receptor, serves as a model. (
  • To date, at least 140 similar structures have been identified and assigned to the voltage gated ion channel (VGIC) superfamily ( Yu and Catterall, 2004 ). (
  • 1 The VGIC superfamily includes calcium channels, chloride channels, potassium channels and sodium channels. (
  • Since 2002, new members of the ion channel protein superfamily have been discovered, and much more has been learned about the previously known members. (
  • The first article provides an overview of the molecular relationships, structure, and function, focusing on aspects that cut across most of the families in the ion channel superfamily. (
  • Members of the superfamily of voltage-gated ion channels are the molecular components underlying electrical excitability in nerves and muscle. (
  • This information may be relevant to several members of the ligand-gated ion channel superfamily. (
  • 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. (
  • Permeation describes the ability of ion channels to selectively determine which ions can move through them. (
  • 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. (
  • Here we explore ion permeation on multimicrosecond timescales using the purpose-built Anton supercomputer. (
  • The molecular understanding of ion permeation is thus a central issue in the study of these ion channels. (
  • 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 [2-3] . (
  • 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. (
  • 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 ). (
  • The ion selectivity of the channel is a property associated with its permeation pathway, normally called the pore. (
  • In addition, because these agents are believed to interact in the ion channel itself, our analysis will provide fundamental information about the characteristics of channel-lining amino acids that influence ion channel gating and permeation. (
  • abstract = "Probes against the retinal cGMP-gated cation channel were generated by PCR amplification of cDNA from rat and bovine retina. (
  • abstract = " Magnesium ions (Mg 2+ ) are divalent cations essential for various cellular functions. (
  • Movement of the voltage-sensor triggers a conformational change of the gate of the conducting pathway, controlling the flow of ions through the channel. (
  • Gating is the process by which ion channels open and close to control the flow of ions. (
  • The flow of ions across the membrane is inhibited by a structurally-diverse class of molecules including tricyclic antidepressants, local anaesthetics and certain transition metals that bind to the transmembrane pore. (
  • Voltage-gated channels allow the selective flow of ions across the hydrophobic lipid bilayer of a cell, opening and closing in response to changes in the voltage across the membrane. (
  • Voltage-gated ion-channels are usually ion-specific, and channels specific to sodium (Na+), potassium (K+), calcium (Ca2+), and chloride (Cl−) ions have been identified. (
  • Voltage-gated sodium channels and calcium channels are made up of a single polypeptide with four homologous domains. (
  • Potassium and calcium are two examples of ions that have to come through ion channels like this. (
  • Phase 2 otherwise known as the 'plateau' phase of the cardiac action potential is maintained by an inward movement of calcium ions and an outward movement of Potassium ions. (
  • Voltage-gated calcium channels ( VGCCs ), also known as voltage-dependent calcium channels ( VDCCs ), are a group of voltage-gated ion channels found in the membrane of excitable cells ( e.g. , muscle , glial cells , neurons , etc.) with a permeability to the calcium ion Ca 2+ . (
  • [1] [2] These channels are slightly permeable to sodium ions , so they are also called Ca 2+ -Na + channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions. (
  • The concentration of calcium (Ca 2+ ions) is normally several thousand times higher outside the cell than inside. (
  • Activation of particular VGCCs allows Ca 2+ to rush into the cell, which, depending on the cell type, results in activation of calcium-sensitive potassium channels , muscular contraction , [4] excitation of neurons, up-regulation of gene expression , or release of hormones or neurotransmitters . (
  • Voltage-gated calcium channels are formed as a complex of several different subunits: α 1 , α 2 δ, β 1-4 , and γ. (
  • There are several different kinds of high-voltage-gated calcium channels (HVGCCs). (
  • [9] VGCCs are subject to rapid inactivation, which is thought to consist of 2 components: voltage-gated (VGI) and calcium-gated (CGI). (
  • Detailed models for electron gating in sodium and potassium ion channels are described and an electron-gating model for calcium oscillators is presented. (
  • Voltage-gated sodium, calcium, and potassium channels generate electrical signals required for action potential generation and conduction and are the molecular targets for a broad range of potent neurotoxins. (
  • Mutations of the á1A subunit of P/Q-type voltage-gated calcium channels are responsible for several inherited disorders affecting humans, including familial hemiplegic migraine, episodic ataxia type 2 and spinocerebellar ataxia type 6. (
  • The leaner mouse also carries a mutation in the alpha(1A) subunit of P/Q-type voltage-gated calcium channels, which results in a severe cerebellar atrophy and ataxia. (
  • The leaner mutation causes reduced calcium ion influx upon activation of P/Q-type voltage-gated calcium channels. (
  • Because of its similarities with human P/Qtype voltage-gated calcium channel mutations, leaner mouse has served as a model for these disorders to aid our understanding of calcium channel function and neurodegeneration associated with calcium channel dysfunction. (
  • 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. (
  • The Department of Molecular Pharmacology offers state-of-the-art methods to study ligand-gated ion channels by electrophysiology and molecular biology techniques. (
  • Natural gates can be altered and augmented using synthetic chemistry and molecular biology to develop channels with completely new functional properties. (
  • This review covers the molecular principles that guide the engineering of light-gated ion channels for applications in biology and medicine. (
  • From these studies a molecular picture of the structural elements important for the activity of voltage-gated ion channels has been established. (
  • We have used multimicrosecond simulations to provide molecular-level descriptions of sodium channel function. (
  • This authoritative and comprehensive volume presents a perspective in the molecular and cellular diversity of membrane ion channels. (
  • Ion channel structure, function and involvement in disease have been exquisitely detailed by traditional electrophysiological and molecular biological methods. (
  • 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. (
  • 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. (
  • A number of ion channels contain transmembrane (TM) α‐helices that contain proline‐induced molecular hinges. (
  • 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. (
  • The recent determination of several crystal structures of voltage-gated ion channels has catalyzed computational efforts of studying these remarkable molecular machines that are able to conduct ions across biological membranes at extremely high rates without compromising the ion selectivity. (
  • Starting from the open crystal structures, we have studied the gating mechanism of these channels by molecular modeling techniques. (
  • Thirdly, collaborators of ours identified new molecular constraints for different states along the gating pathway. (
  • 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. (
  • 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. (
  • Coupling between the activation gate and sensors of physiological stimuli during ion channel activation is an important, but not well-understood, molecular process. (
  • The opening of these ion channels includes three general molecular processes: activation of the sensor, propagation of the conformational changes in the sensor to the pore, and the opening of the pore. (
  • Currents leaking through VSDs are called omega or gating pore currents. (
  • Gating pore currents have recently been shown to cause periodic paralysis phenotypes. (
  • These toxins may thus modulate gating pore currents. (
  • The purpose of the present review is to summarize existing knowledge of the pathophysiology, biophysics, and pharmacology of gating pore currents and to serve as a guide for future studies aimed at improving our understanding of gating pores and their pathophysiological roles. (
  • For example, if you want to measure the sodium gating currents, how do you do it? (
  • more precisely, measure the gating currents. (
  • the gating current is different than the direction of the sodium currents. (
  • We study the voltage-sensing mechanism of several ion channels by expressing cloned channels in Xenopus oocytes and measuring ion and gating currents with several electrophysiological methods such as the two-electrode voltage clamp and patch-clamp techniques. (
  • Voltage-gated K + currents in β-cells. (
  • Voltage-gated K + currents recorded under control conditions and in the presence of 1 or 10 mmol/l TEA. (
  • Voltage-gated K + currents recorded in the absence and presence of 100 nmol/l stromatoxin. (
  • Voltage-gated Na + -currents. (
  • Voltage-gated Ca 2+ currents. (
  • 200 mM ethanol did not modulate channel currents, nor did 100% nitrous oxide. (
  • Our results provide the first evidence that quantum mechanical properties are needed to explain a fundamental biological property such as ion-selectivity in trans-membrane ion-currents and the effect on gating kinetics and shaping of classical conductances in electrically excitable cells. (
  • Ion channels are desirable therapeutic targets, yet ion channel-directed drugs with high selectivity and few side effects are still needed. (
  • Residues spacefilled in red represent residues in the selectivity filter accessible to cysteine modification in closed CNG channels. (
  • This channel's selectivity filter exhibits an EEEE ring sequence, characteristic of mammalian Ca 2+ , not Na + , channels. (
  • More precisely, these ordered water molecules contribute to lower the energy barriers encountered by the permeant ion when it crosses the hydrophobic constriction barriers that are located along the selectivity filter. (
  • The permeating ions occupy two preferential positions in the most constricted region of the pore that hosts the selectivity filter. (
  • Anion/cation selectivity is a critical property of ion channels and underpins their physiological function. (
  • Recently, there have been numerous mutagenesis studies, which have mapped sites within the ion channel-forming segments of ligand-gated ion channels that are determinants of the ion selectivity. (
  • In particular, the dominant factor determining anion/cation selectivity seems to be the sign and exposure of charged amino acids lining the selectivity filter region of the open channel. (
  • In addition, the minimum pore diameter, which can be influenced by the presence of a local proline residue, also makes a contribution to such ion selectivity in LGICs with smaller diameters increasing anion/cation selectivity and larger ones decreasing it. (
  • Despite their differences in ion selectivity and gating capabilities, voltage-gated channels in general share a number of structural features. (
  • The introduction of three mutations, Y221A (Y-3′A), E222P (E-2′P) and N224R (N0′R), at the selectivity filter and one, A237T (A13′T), at the hydrophobic gate, converted GLIC into an anion channel. (
  • It is thought that the first 4 arginines account for the gating current, moving toward the extracellular solvent upon channel activation in response to membrane depolarization. (
  • They are composed of a large extracellular glycosylated N-terminal ligand-binding domain, followed by three hydrophobic transmembrane regions which form the ionic channel, followed by an intracellular region of variable length. (
  • Optimised set of configurations of the Ser230 and Thr226 side chains can maximise the permeant ion density at five levels in the pore, from its extracellular to its intracellular end. (
  • Extracellular zinc ion inhibits ClC-0 chloride channels by facilitating slow gating. (
  • Extracellular Zn2+ was found to reversibly inhibit the ClC-0 Cl- channel. (
  • Extracellular Zn2+ facilitated the slow-gating process at all temperatures, but the Q10 did not change. (
  • These results together indicate that extracellular Zn2+ inhibits ClC-0 by facilitating the slow-gating process. (
  • Voltage-gated ion channels are generally composed of several subunits arranged in such a way that there is a central pore through which ions can travel down their electrochemical gradients. (
  • these four domains are part of a single α-subunit in the case of most Na+ and Ca2+ channels, whereas there are four α-subunits, each contributing one transmembrane domain, in most K+ channels. (
  • All known sequences of subunits from neurotransmitter-gated ion-channels are structurally related. (
  • With a multisubunit ion channel, where the subunits have multiple transmembrane helices, how do you tell which of a subunit's helices is the porelining helix? (
  • For simplicity, this figure shows two of the four subunits comprising CNG channels. (
  • Left: Cartoon representation of the GLIC ion channel viewed from the side (for clarity only two subunits are shown). (
  • Genome annotation, phylogenetic analysis and comparison of the cysLGIC subunits with their counterparts in insects reveals that the T. urticae genome encodes for a high number of glutamate- and histamine-gated chloride channel genes (GluCl and HisCl) compared to insects. (
  • We further reveal the accumulation of known and novel mutations in different GluCl channel subunits (Tu_GluCl1 and Tu_GluCl3) associated with abamectin resistance in T. urticae, and provide genetic evidence for their causality. (
  • Voltage-gated Na + and Ca 2+ channels are composed of a single pore-forming polypeptide (the alpha subunit), plus various auxiliary subunits. (
  • The alpha subunits of these channels contain four repeats of a core motif, which consists of six predicted transmembrane regions, S1-S6. (
  • The α 1 subunit forms the ion conducting pore while the associated subunits have several functions including modulation of gating. (
  • This arrangement is analogous to a homo-tetramer formed by single-domain subunits of voltage-gated potassium channels (that also each contain 6 TM helices). (
  • Similar to Kv channels, the BK channels are homotetramers with the central pore formed by S5 to S6 transmembrane segments from all four subunits and voltage sensor domains (VSDs) containing S1-S4 transmembrane segments. (
  • Here we determine crystal structures of the ethanol-sensitized variant in the absence and presence of ethanol and related modulators, which bind in a transmembrane cavity between channel subunits and may stabilize the open form of the channel. (
  • We describe an almost barrier-less three-ion conduction mechanism involving competing knock-on and "pass-by" processes, intimately linked to signature glutamate ring protonation and structural isomerizations. (
  • In this thesis, polyunsaturated fatty acids (PUFAs) were used as key substances to study a new pharmacological mechanism for how to induce opening of voltage-gated potassium (Kv) channels, and how this possibly can protect against epileptic activity. (
  • Both the identified PUFA-action site and the mechanism by which PUFAs induce channel opening are novel and could potentially be very useful in future drug design of compounds targeting neuronal and cardiac excitability. (
  • Recent developments in automated electrophysiological platforms, in combination with more traditional methods, provide the tools for screening, profiling and mechanism-of-action studies in ligand-gated ion channels. (
  • The massive increase observed under some pathological conditions, especially in brain, has been interpreted as a protective mechanism possibly operative on ion channels, which in some cases is of stimulatory nature and in other cases inhibitory. (
  • All these results point to a gating mechanism where the S4 helix undergoes a secondary structure transformation during gating. (
  • Understanding ion channel gating has been a goal of researchers since Hodgkin and Huxley's classic publication in 1952, but the gating mechanism has remained elusive. (
  • Introducing the electron as a gating agent requires amplification, but until now there has been no appropriate mechanism for amplification. (
  • Hydrophobic alkaloid toxins and related lipid-soluble toxins act at intramembrane sites and alter voltage-dependent gating of sodium channels via an allosteric mechanism. (
  • The voltage-sensor trapping mechanism may be a common mode of action for polypeptide gating modifier toxins acting on all of the voltage-gated ion channels. (
  • This study revealed the role of each Mg 2+ -binding site in MgtE gating, underlying the mechanism of cellular Mg 2+ homeostasis. (
  • The overall goal of this project is to determine the mechanism and site of neurotoxin action on ligand-gated ion channels. (
  • The opening and closing of the channels are triggered by changing ion concentration, and hence charge gradient, between the sides of the cell membrane. (
  • This movement of ions down their concentration gradients subsequently generates an electric current sufficient to depolarize the cell membrane. (
  • PIP2 is a cell membrane lipid, and its role in gating ion channels represents a novel role for the molecule. (
  • These ions are too big for the cell membrane to easily let pass through. (
  • If the membrane is less negative, the fast sodium ions become inactive and insensitive to opening, and so this leads to a slight response to excitation of the cell membrane thus leading to a lower Vmax. (
  • In excitable cells, ions permeate the cell membrane through ionic channels, some of which open and close in response to changes in the potential difference across the membrane. (
  • In the vibrant field of optogenetics, optics and genetic targeting are combined to commandeer cellular functions, such as the neuronal action potential, by optically stimulating light-sensitive ion channels expressed in the cell membrane. (
  • Cyclic nucleotides are small ligands used to control the gating of CNG channels. (
  • A subclass of ion channels that open or close in response to the binding of specific Ligands . (
  • 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 ). (
  • 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. (
  • 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. (
  • The lipid binds in a well-defined ligand binding site in the transmembrane domain and causes the helices to splay opening the channel. (
  • For TRPV5, binding of PIP2 to a site in the transmembrane domain caused a conformational change that appeared to open the conduction pathway, suggesting the channel is classically lipid-gated. (
  • K2p: PA directly activates TREK-1 potassium channels through a putative site in the transmembrane domain. (
  • Similarly to voltage‐gated K + channels, CNG channels are tetramers where each subunit contains six transmembrane domains, intracellular N ‐ and C ‐termini, positive charges in the fourth transmembrane domain (S4), and a P‐loop lining the pore of the channel. (
  • 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. (
  • Cyclic nucleotide‐gated (CNG) ion channels are activated by cAMP or cGMP, crucial intracellular messenger molecules that regulate a wide variety of physiological activities. (
  • CNG channels are also found in other tissues including brain and sperm, where they may contribute to physiological functions including pacemaking, synaptic transmission and chemosensation. (
  • It describes the structure of the brain protein, called a ligand-gated ion channel , that is a key enabler of many of the primary physiological and behavioral effects of alcohol. (
  • Polyunsaturated fatty acids (PUFAs) act on most ion channels, thereby having significant physiological and pharmacological effects. (
  • This mapping of functional PUFA sites can form the basis for physiological and pharmacological modifications of voltage-gated ion channels. (
  • C2 symmetry is particularly pronounced in the dataset collected from nanodisc-reconstituted TRPV2, which better approximates the physiological environment of the channel. (
  • With strong cytoplasmic buffering and Ca 2+ flux sufficiently reduced by applied voltage, both activation and inhibition of InsP 3 R channel gating by physiological levels of [Ca 2+ ] ER were completely abolished. (
  • The book includes reviews of the channel genome, the physiological bases of targeting ion channels in disease, the unique technologies developed for ion channel drug discovery, and the increasingly important role of ion channel screening in cardiac risk assessment. (
  • 1. Baron A, Lingueglia E. (2015) Pharmacology of acid-sensing ion channels - Physiological and therapeutical perspectives. (
  • Many ion channels contain distinct structural domains that function as the sensor of physiological stimuli and the pore that allows ions to flow across the membrane. (
  • Pentameric ligand-gated ion channels (pLGICs) are key players in the early events of electrical signal transduction at chemical synapses. (
  • pLGICs (pentameric ligand-gated ion channels) are a family of structurally homologous cation and anion channels involved in neurotransmission. (
  • PA lipids were proposed to non-specifically gated a homologous channel from bacteria KvAP, but those experiments did not rule out the anionic lipid phosphatidylglycerol from contributing specifically to gating. (
  • D66 is important for Ca 2+ binding in NaK, as the homologous aspartate in CNG channels. (
  • Crystallographic structural studies of a potassium channel have shown that, when a potential difference is introduced over the membrane, the associated electric field induces a conformational change in the potassium channel. (
  • The movement of 10-12 of these protein-bound positive charges triggers a conformational change that opens the channel. (
  • Voltage-gated ion channels can either be inactivated from this open state by an additional conformational change which leads to a nonconducting state of the channel, or they may be deactivated by a repolarized membrane potential. (
  • These simulations have uncovered a high degree of protein flexibility, with conformational fluctuations in the pore domain involving residues central to slow-type inactivation, leading to gate collapse, helix bending, filter disruption, and changes in lipid-facing fenestrations linked to Na v drug pathways. (
  • We have observed conformational changes in the pore domain leading to asymmetrical collapses of the activation gate, similar to proposed inactivated structures of Na v Ab, with helix bending involving conserved residues that are critical for slow inactivation. (
  • The determination of structural models of the various stable states of an ion channel is a key step toward the characterization of its conformational dynamics. (
  • Similarly, mutations can also affect the conformational free-energy landscape of ion channels in such a way that the occupancy of a particular conformation is markedly favored or disfavored. (
  • Moreover, the data offers further insights into the allosteric coupling between the RTx-binding site and the activation gates in TRPV2, confirms the critical role of the S4-S5 linker π-helix (S4-S5 π-hinge ) in ligand-dependent gating of TRPV2, and provides a glimpse of the conformational landscape of TRPV2 gating. (
  • These structures suggest specific conformational transitions that may occur during channel activation. (
  • In the GLIC structure, the Glu222 carboxylate groups are flexible and continuously exchange between alternative conformations, thus facilitating ion transport. (
  • The mutated GLIC (GLIC4) became insensitive to the anaesthetics propofol and etomidate, as well as the channel blocker picrotoxin. (
  • 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. (
  • The fifth and sixth transmembrane segments (S5 and S6) and pore loop serve the principal role of ion conduction, comprising the gate and pore of the channel, while S1-S4 serve as the voltage-sensing region. (
  • 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. (
  • 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. (
  • 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. (
  • 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. (
  • Under normal conditions, HCN channels are poorly expressed outside the cardiac pacemaking and conduction system [ 11 , 18 - 20 ] , but it changes during cardiac disease. (
  • If the resting membrane becomes too positive then sodium channels will not be able to flow through effectively and so will cause the delay of conduction through the heart. (
  • Cell membranes are generally impermeable to ions, thus they must diffuse through the membrane through transmembrane protein channels. (
  • The main functional part of the voltage-sensitive protein domain of these channels generally contains a region composed of S3b and S4 helices, known as the "paddle" due to its shape, which appears to be a conserved sequence, interchangeable across a wide variety of cells and species. (
  • In the case of the bacterial member ELIC, a cysteamine-gated channel from Erwinia chrisanthemi , a structural model of the protein in the absence of activating ligand (and thus, conceivably corresponding to the closed state of this channel) has been previously generated. (
  • Structure and dynamics of voltage-gated ion channels, in particular the motion of the S4 helix, is a highly interesting and hotly debated topic in current membrane protein research. (
  • The CGI component is attributed to the binding of the Ca 2+ -binding signaling protein calmodulin (CaM) to at least 1 site on the channel, as Ca 2+ -null CaM mutants abolish CGI in L-type channels. (
  • The CFTR gene encodes an ATP-binding cassette (ABC) transporter that functions as a low conductance Cl(-)-selective channel gated by cycles of ATP binding and hydrolysis at its nucleotide-binding domains (NBDs) and regulated tightly by an intrinsically disordered protein segment distinguished by multiple consensus phosphorylation sites termed. (
  • Protein which is a component of a voltage-gated channel. (
  • This task was undertaken by the Nomenclature Committee of the International Union of Pharmacology (IUPHAR) in 1999, and the IUPHAR Compendium of Voltage-Gated Ion Channels 2002 was published 3 years later as a bound volume by IUPHAR Media. (
  • And if we are starting the potassium channel changing current. (
  • this is one of the example of the Shaker potassium channel. (
  • You can block the potassium channel and you can measure the gating current. (
  • The majority of ion channels fall into two broad categories: voltage-gated ion channels (VGIC) and ligand-gated ion channels (LGIC). (
  • Ligand-gated ion channels (LGIC) play a central role in inter-cellular communication. (
  • Once a LGIC causes a channel to open and the membrane depolarizes, the depolarization activates what? (
  • Dietary glycine prevents peptidoglycan polysaccharide-induced reactive arthritis in the rat: role for glycine-gated chloride channel. (
  • This work supports the hypothesis that glycine prevents reactive arthritis by blunting cytokine release from macrophages by increasing chloride influx via a glycine-gated chloride channel. (
  • Lipid-gated ion channels are a class of ion channels whose conductance of ions through the membrane depends directly on lipids. (
  • PIP2 regulates the conductance of most TRP channels either positively or negatively. (
  • Activation of large conductance Ca2+-activated K+ channels is controlled by both cytoplasmic Ca2+ and membrane potential. (
  • The magnitude of the current across the membrane depends on the density of channels, the conductance of the open channel, and how often the channel spends in its open position or its open probability. (
  • One of the models had a conductance consistent with the experimental data and was proposed to represent the biological active state of the channel. (
  • At this phase the Sodium Channels open which caused a rapid influx of Sodium ions into the cell. (
  • At baseline -85mV the Sodium ion channels are not open, however when excited they open, causing an influx of sodium ions. (
  • Voltage-gated ion channels play fundamental roles in neuronal excitability and therefore dysfunctional channels can cause disease. (
  • Instead of blocking the ion conducting pore to modify neuronal and cardiac activity we have proposed that medical drugs can target the voltage sensor. (
  • Making nAChR light sensitive allowed the researchers to study channel kinetics without considering molecules that stimulate them, a previously insurmountable limitation. (
  • Voltage-gated ion channels are key molecules for the generation of electrical signals in cells. (
  • In a set of four inter-related volumes the Ion Channels FactsBook provides a comprehensive framework of facts about channel molecules central to electrical signalling phenomena of living cells. (
  • To better understand the function of the organised water molecules observed in the pore, it was necessary to identify the monovalent ion binding sites in the transmembrane pore. (
  • As the quest for new selective molecules targeting sodium channels for the treatment of chronic pain continues, Axon Medchem intends to expand its range of sodium channel modulators accordingly. (
  • Discover Bioactive Small Molecules for Ion Channels Research. (
  • And how does that relate to ligand-gated channels in general? (
  • The voltage-gated Na+ channels are still CLOSED, but it is the **LIGAND-GATED channels & **passive ion movement that is responsible for creating these GRADED potentials Graded Potentials -->Changes in the membrane potential that are confined to a relatively SMALL region of the plasma membrane. (
  • 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. (
  • Using modified potassium channels - dubbed SPARK (synthetic photoisomerizable azobenzene-regulated K+) - they have studied action potential firing of hippocampal neurons. (
  • In photoreceptors and olfactory neurons, CNG channels play an essential role in transducing sensory stimuli into electrical and chemical responses. (
  • Subunit stoichiometry of CNG channels in photoreceptors and olfactory neurons. (
  • 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. (
  • 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. (
  • 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. (
  • Bittner KC, Andrasfalvy BK, Magee JC (2012) Ion channel gradients in the apical tuft region of CA1 pyramidal neurons. (
  • Cannon RC, O'Donnell C, Nolan MF (2010) Stochastic ion channel gating in dendritic neurons: morphology dependence and probabilistic synaptic activation of dendritic spikes. (
  • Dorval AD Jr, White JA (2005) Channel noise is essential for perithreshold oscillations in entorhinal stellate neurons. (
  • Unlike small-molecule inhibitors, antibodies are highly selective for target antigens but mostly fail to antagonize ion channel functions. (
  • These previously undescribed effects on cation-selective channels may provide additional insight into the central actions of these toxic agents. (
  • Anesthetic sites and allosteric mechanisms of action on Cys-loop ligand-gated ion channels. (
  • BK channels are activated by membrane voltage and intracellular Ca 2+ via allosteric mechanisms with coupling among the activation gate and sensors quantitatively defined, providing an excellent model system for studying sensor-gate coupling. (
  • 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. (
  • PUFA site 3: The intracellular gate. (
  • Finally, the presence of a reservoir of counter-ions located at the intracellular mouth of the pore might help in either retaining the permeant ion or creating a favourable corridor through it. (
  • generously note, old experiments using TEA + and analogues to block K channels ( Armstrong, 1971 ) suggested that the activation gate is inside and that the search should be in the intracellular segments of the sequence. (
  • Mg 2+ homeostasis is maintained through Mg 2+ channels such as MgtE, a prokaryotic Mg 2+ channel whose gating is regulated by intracellular Mg 2+ levels. (
  • The functionality of voltage-gated ion channels is attributed to its three main discrete units: the voltage sensor, the pore or conducting pathway, and the gate. (
  • Our data offers insights into a gating pathway in TRPV2 involving symmetry transitions. (
  • Three orthologues of the insect γ-aminobutyric acid (GABA)-gated chloride channel gene Rdl were detected. (
  • The apparent on and off rates of the inhibition were highly temperature sensitive, suggesting an effect of Zn2+ on the slow gating (or inactivation) of ClC-0. (
  • Our initial studies in vitro demonstrate enhanced binding of the compounds to the sodium channel and increased inhibition of prostate cancer cell growth in culture and in soft agarose compared with phenytoin. (
  • 2018) Inhibition of acid-sensing ion channels by diminazene and APETx2 evoke partial and highly variable antihyperalgesia in a rat model of inflammatory pain. (
  • For example, in the case of (wild-type) neurotransmitter-gated channels, the binding of the natural neurotransmitter strongly stabilizes the desensitized state (e.g., ref. 1 ), whereas the absence of neurotransmitter or the binding of a competitive antagonist keeps the channel mostly closed ( 2 , 3 ). (
  • Curiously, the obtained structural models turned out to be nearly indistinguishable from the model of the wild-type channel in the absence of bound agonist. (
  • Structural models of ligand-gated ion channels: sites of action for anesthetics and ethanol. (
  • One difficulty in studying sensor-gate coupling is to distinguish whether a structural perturbation alters the function of the sensor, the gate, or their coupling. (
  • These results suggest a structural arrangement of the inner pore of BK channels differing from that in other voltage gated channels. (
  • These channels are built on a common structural motif containing six transmembrane segments and a pore loop. (
  • By mutating and modifying the channel at strategic positions the PUFA-action site was localized to a lipid-exposed surface close to the channel's voltage sensor. (
  • We also showed that PUFAs induce channel opening by electrostatically facilitating a final voltage-sensor movement. (
  • Binding to this site leads to an opening of the channel via an electrostatic attraction between the negatively charged PUFA and the positively charged voltage sensor. (
  • 1] The Voltage Sensor in Voltage-Dependent Ion Channels. (
  • Firstly, by applying a membrane potential, initial stages of the closing of the channel were captured, manifested in a secondary-structure change in the voltage-sensor. (
  • the other is to regulate coupling among the activation gate, voltage sensor, and Ca 2+ binding via electrostatic interactions with E321/E324 located in the cytosolic side of S6 in a neighboring subunit, resulting in a shift of the voltage dependence of channel opening and increased Ca 2+ sensitivity. (
  • The voltage sensor domain consists of the S1-S4 segments, with positively charged residues in the S4 segment serving as gating charges. (
  • We further focus on the mechanisms of FFA modulation operating on voltage-gated and ligand-gated ion channel function, contrasting the still conflicting evidence on direct vs. indirect mechanisms of action. (
  • Dudman JT, Nolan MF (2009) Stochastically gating ion channels enable patterned spike firing through activity-dependent modulation of spike probability. (
  • Very recently, naturally occurring light-gated cation channels have been discovered. (