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 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.
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.
A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.
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.
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 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.
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 voltage-gated sodium channel subtype found widely expressed in nociceptive primary sensory neurons. Defects in the SCN9A gene, which codes for the alpha subunit of this sodium channel, are associated with several pain sensation-related disorders.
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 voltage-gated sodium channel subtype found widely expressed in neurons of the central and peripheral nervous systems. Defects in the SCN8A gene which codes for the alpha subunit of this sodium channel are associated with ATAXIA and cognitive deficits.
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.
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 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 voltage-gated sodium channel subtype found in neuronal tissue that mediates the sodium ion PERMEABILITY of excitable membranes.
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.
A voltage-gated sodium channel subtype found in the neurons of the NERVOUS SYSTEM and DORSAL ROOT GANGLIA. It may play a role in the generation of heat and mechanical pain hypersensitivity.
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 class of drugs that stimulate sodium influx through cell membrane channels.
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.
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.
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.
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.
Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.
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 class of drugs that act by selective inhibition of calcium influx through cellular membranes.
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 inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS.
The ability of a substrate to allow the passage of ELECTRONS.
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).
Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.
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.
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.
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.
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.
Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.
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.
The rate dynamics in chemical or physical systems.
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.
A benzoate-cevane found in VERATRUM and Schoenocaulon. It activates SODIUM CHANNELS to stay open longer than normal.
A voltage-gated sodium channel beta subunit abundantly expressed in SKELETAL MUSCLE; HEART; and BRAIN. It non-covalently associates with voltage-gated alpha subunits. Defects in the SCN1B gene, which codes for this beta subunit, are associated with generalized epilepsy with febrile seizures plus, type 1, and Brugada syndrome 5.
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.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
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 subclass of sodium channel blockers that are specific for EPITHELIAL SODIUM CHANNELS.
Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.
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.
Potassium channels whose activation is dependent on intracellular calcium concentrations.
A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.
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 voltage-gated sodium channel beta subunit subtype that non-covalently associates with voltage-gated alpha subunits. Defects in the SCN3B gene which codes for this beta subunit are associated with Brugada syndrome 7.
Regularly spaced gaps in the myelin sheaths of peripheral axons. Ranvier's nodes allow saltatory conduction, that is, jumping of impulses from node to node, which is faster and more energetically favorable than continuous conduction.
Established cell cultures that have the potential to propagate indefinitely.
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.
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 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.
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.
CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.
Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.
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.
A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.
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 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.
A voltage-gated sodium channel beta subunit that binds covalently to voltage-gated alpha subunits.
The active insecticidal constituent of CHRYSANTHEMUM CINERARIIFOLIUM flowers. Pyrethrin I is the pyretholone ester of chrysanthemummonocarboxylic acid and pyrethrin II is the pyretholone ester of chrysanthemumdicarboxylic acid monomethyl ester.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
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.
Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties.
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 voltage-gated sodium channel beta subunit subtype that covalently associates with voltage-gated alpha subunits. Defects in the SCN4B gene, which codes for this beta subunit, are associated with long QT syndrome-10.
Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
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.
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)
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.
A superorder of CEPHALOPODS comprised of squid, cuttlefish, and their relatives. Their distinguishing feature is the modification of their fourth pair of arms into tentacles, resulting in 10 limbs.
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.
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.
Insects of the order Dictyoptera comprising several families including Blaberidae, BLATTELLIDAE, Blattidae (containing the American cockroach PERIPLANETA americana), Cryptocercidae, and Polyphagidae.
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.
A peripheral arterial disease that is characterized by the triad of ERYTHEMA, burning PAIN, and increased SKIN TEMPERATURE of the extremities (or red, painful extremities). Erythromelalgia may be classified as primary or idiopathic, familial or non-familial. Secondary erythromelalgia is associated with other diseases, the most common being MYELOPROLIFERATIVE DISORDERS.
Arthropods of the order Scorpiones, of which 1500 to 2000 species have been described. The most common live in tropical or subtropical areas. They are nocturnal and feed principally on insects and other arthropods. They are large arachnids but do not attack man spontaneously. They have a venomous sting. Their medical significance varies considerably and is dependent on their habits and venom potency rather than on their size. At most, the sting is equivalent to that of a hornet but certain species possess a highly toxic venom potentially fatal to humans. (From Dorland, 27th ed; Smith, Insects and Other Arthropods of Medical Importance, 1973, p417; Barnes, Invertebrate Zoology, 5th ed, p503)
Elements of limited time intervals, contributing to particular results or situations.
Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.
A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.
Compounds that either stimulate the opening or prevent closure of EPITHELIAL SODIUM ION CHANNELS.
Sodium or sodium compounds used in foods or as a food. The most frequently used compounds are sodium chloride or sodium glutamate.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Use of electric potential or currents to elicit biological responses.
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.
A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
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.
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.
Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of MYOTONIC DISORDERS.
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.
A ubiquitous sodium salt that is commonly used to season food.
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 voltage-gated potassium channel that is expressed primarily in the HEART.
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 parts of a macromolecule that directly participate in its specific combination with another molecule.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate.
The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.
Compounds based on an 8-membered heterocyclic ring including an oxygen. They can be considered medium ring ethers.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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.
A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)
Toxic or poisonous substances elaborated by marine flora or fauna. They include also specific, characterized poisons or toxins for which there is no more specific heading, like those from poisonous FISHES.
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 study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.
Venoms from jellyfish; CORALS; SEA ANEMONES; etc. They contain hemo-, cardio-, dermo- , and neuro-toxic substances and probably ENZYMES. They include palytoxin, sarcophine, and anthopleurine.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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 subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Proteins prepared by recombinant DNA technology.
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)
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.
Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.
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 hollow, muscular organ that maintains the circulation of the blood.
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 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.
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 fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.
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.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
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.
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.
The physical characteristics and processes of biological systems.
A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.
Proteins obtained from species in the class of AMPHIBIANS.
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 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.
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)
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.
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 genus of fish, in the family GYMNOTIFORMES, capable of producing an electric shock that immobilizes fish and other prey. The species Electrophorus electricus is also known as the electric eel, though it is not a true eel.
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.
Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.
A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.
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.
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 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.
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).
A variety of neuromuscular conditions resulting from MUTATIONS in ION CHANNELS manifesting as episodes of EPILEPSY; HEADACHE DISORDERS; and DYSKINESIAS.
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.
Contractile tissue that produces movement in animals.
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.
Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates.
Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.
Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.
A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.
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.
A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.
Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics.
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.
Polycyclic ethers produced by Gambierdiscus (DINOFLAGELLATES) from gambiertoxins, which are ingested by fish which in turn may be ingested by humans who are susceptible to the CIGUATERA POISONING.
The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.
A family of membrane-associated proteins responsible for the attachment of the cytoskeleton. Erythrocyte-related isoforms of ankyrin attach the SPECTRIN cytoskeleton to a transmembrane protein (ANION EXCHANGE PROTEIN 1, ERYTHROCYTE) in the erythrocyte plasma membrane. Brain-related isoforms of ankyrin also exist.
An autosomal dominant defect of cardiac conduction that is characterized by an abnormal ST-segment in leads V1-V3 on the ELECTROCARDIOGRAM resembling a right BUNDLE-BRANCH BLOCK; high risk of VENTRICULAR TACHYCARDIA; or VENTRICULAR FIBRILLATION; SYNCOPAL EPISODE; and possible sudden death. This syndrome is linked to mutations of gene encoding the cardiac SODIUM CHANNEL alpha subunit.
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 electrical properties, characteristics of living organisms, and the processes of organisms or their parts that are involved in generating and responding to electrical charges.
A heterogenous group of inherited disorders characterized by recurring attacks of rapidly progressive flaccid paralysis or myotonia. These conditions have in common a mutation of the gene encoding the alpha subunit of the sodium channel in skeletal muscle. They are frequently associated with fluctuations in serum potassium levels. Periodic paralysis may also occur as a non-familial process secondary to THYROTOXICOSIS and other conditions. (From Adams et al., Principles of Neurology, 6th ed, p1481)
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 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.
A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)
The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of Bellini) which opens on the summit of the papilla.
CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.
Venoms from mollusks, including CONUS and OCTOPUS species. The venoms contain proteins, enzymes, choline derivatives, slow-reacting substances, and several characterized polypeptide toxins that affect the nervous system. Mollusk venoms include cephalotoxin, venerupin, maculotoxin, surugatoxin, conotoxins, and murexine.
The order Actiniaria, in the class ANTHOZOA, comprised of large, solitary polyps. All species are carnivorous.
Compounds based on N-phenylacetamide, that are similar in structure to 2-PHENYLACETAMIDES. They are precursors of many other compounds. They were formerly used as ANALGESICS and ANTIPYRETICS, but often caused lethal METHEMOGLOBINEMIA.
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.
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.
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.
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.
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.
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.
A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.
A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.
Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).
A surface anesthetic that acts by preventing transmission of impulses along NERVE FIBERS and at NERVE ENDINGS.
A highly variable species of the family Ranidae in Canada, the United States and Central America. It is the most widely used Anuran in biomedical research.
A clinically diverse group of epilepsy syndromes characterized either by myoclonic seizures or by myoclonus in association with other seizure types. Myoclonic epilepsy syndromes are divided into three subtypes based on etiology: familial, cryptogenic, and symptomatic (i.e., occurring secondary to known disease processes such as infections, hypoxic-ischemic injuries, trauma, etc.).
An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.
Refers to animals in the period of time just after birth.
An impulse-conducting system composed of modified cardiac muscle, having the power of spontaneous rhythmicity and conduction more highly developed than the rest of the heart.
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.
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.
CALCIUM CHANNELS located in the neurons of the brain.
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.
"Voltage-gated", also called "voltage-sensitive" and "voltage-dependent" sodium channel also known as "VGSCs" or "Nav channel" ... Nav1 and Nav2), whereas vertebrate Nav channels are of the Nav1 family. Sodium-channel proteins in the mammalian brain are ... of some voltage gated sodium channels in a very powerful and reversible manner, without affection of other ion channels. " ... April 2012). "Voltage-Gated Sodium Channels at 60: Structure, Function, and Pathophysiology". The Journal of Physiology. 590 ( ...
"Sodium Channel NaV1.5 Expression is Enhanced in Cultured Adult Rat Skeletal Muscle Fibers, The Journal of Membrane Biology" on ... Beta 3: an additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct ... Immunocytochemical localization of the mammalian voltage-dependent sodium channel using polyclonal antibodies against the ... lp/springer_journal/sodium-channel-nav1-5-expression-is-enhanced-in-cultured-adult-rat-lAZWCBiJ8J ...
Your top supplier for voltage-gated Na+ channel research! ... 3 Mammalian sodium channels are heterotrimers, composed of a ... Home › Products › Ion Channels › Na+ ChannelsVoltage-Gated Na+ Channels › Antibodies to NaV Channels ... Voltage-gated sodium channels (NaV) are essential for the generation of action potentials and for cell excitability.1 To date, ... Peptide CKRRSETTAETFTE, corresponding to amino acid residues 43-56 of rat β1 subunit of voltage-gated Na+ channels (Accession ...
Your top supplier for voltage-gated sodium channel research! ... Mammalian sodium channels are heterotrimers, composed of a ... Voltage-gated sodium channels (NaV) are essential for the generation of action potentials and for cell excitability.1 NaV ... Sodium channels in the adult central nervous system and heart contain β1 through β4 subunits, whereas sodium channels in adult ... Alternative Name BII, Brain type II Na+ channel, Sodium channel protein type 2 subunit alpha ...
... anatomically specialized regions which contain very high densities of sodium ion (Na+) channels. Therefore, saltatory ... This localized concentration of Na+ channels resembles in structure the ion channel organization at the nodes of Ranvier, yet ... This localized concentration of Na+ channels resembles in structure the ion channel organization at the Nodes of Ranvier, yet ... By investigating the efficiency of AP propagation over Nav1.8 channels, we find however that the specific inactivation ...
"Voltage-gated", also called "voltage-sensitive" and "voltage-dependent" sodium channel also known as "VGSCs" or "Nav channel" ... Nav1 and Nav2), whereas vertebrate Nav channels are of the Nav1 family. Sodium-channel proteins in the mammalian brain are ... of some voltage gated sodium channels in a very powerful and reversible manner, without affection of other ion channels. " ... April 2012). "Voltage-Gated Sodium Channels at 60: Structure, Function, and Pathophysiology". The Journal of Physiology. 590 ( ...
µ and µO-CTX are two isoforms that specifically target voltage-gated sodium channels. These, by inducing the entrance of sodium ... In this review, we describe the current knowledge of µ-CTX interacting with the different sodium channels subtypes, the ... Hyperexcitability and mutations of sodium channels are responsible for perception and transmission of inflammatory and ... Mahdavi, S.; Kuyucak, S. Molecular dynamics study of binding of µ-conotoxin GIIIA to the voltage-gated sodium channel Nav1. 4. ...
Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic ... Review of the inherited pain syndromes associated with mutations in the NaV1.7 sodium channel. PubMedCrossRefGoogle Scholar ... Devor M, Govrin-Lippmann R, Angelides K. Na + channel immunolocalization in peripheral mammalian axons and changes following ... Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev. 2005;57:397-409.PubMed ...
Heterologous Expression of Sodium Channels. A recombinant human NaV1.5 sodium channel cDNA in a mammalian expression plasmid ( ... Figure 8. Biophysical effects of lidocaine on NaV1. 5-F1760A channels. (A) Current-voltage relationships in the absence and ... Propranolol blocks cardiac and neuronal voltage-gated sodium channels. Dao W. Wang1,2, Akshitkumar M. Mistry1, Kristopher M. ... Voltage-gated sodium channels are established pharmacological targets for local anesthetics and many other drugs with shared ...
Such functions include protease inhibitors, membrane pore formation, ion channel blockers and metal binding proteins. Many of ... Toxin-like functions were revealed using ClanTox, a statistical machine-learning predictor trained on ion channel inhibitors ... Actions of sea anemone type 1 neurotoxins on voltage-gated sodium channel isoforms. Toxicon 2009, 54, 1102-1111. [Google ... The analysis of neurotoxin (Nav1) evolution exposed extensive genomic expansion of this region [42]. Gene expansion has shaped ...
... and pseudo-tetrameric P-loop channels are used to elaborate homology models of mammalian voltage-gated sodium channels with ... ... Voltage-gated sodium channels belong to the superfamily of voltage-gated cation channels. Their structure is based on domains ... the α subunit of the major cardiac voltage-gated sodium channel. This channel forms a protein complex including one or two ...
The voltage-gated sodium channel Na(v)1.9 is an effector of peripheral inflammatory pain hypersensitivity. J Neurosci. 2006;26( ... A quantitative analysis of intron effects on mammalian gene expression. RNA. 2003;9(5):607-617.. View this article via: PubMed ... Functional analysis of stably expressed human Nav1. Biophys J. 2012;102:527a. ... Ahern CA, Payandeh J, Bosmans F, Chanda B. The hitchhikers guide to the voltage-gated sodium channel galaxy. J Gen Physiol. ...
CK2 was further found to directly phosphorylate the voltage gated sodium channel NAv1, thereby enhancing its binding to ankyrin ... Ceglia I., Flajolet M., Rebholz H. Predominance of CK2α over CK2α′ in the mammalian brain. Mol. Cell. Biochem. 2011;356:169-175 ... CK2 activity is required for the interaction of FGF14 with voltage-gated sodium channels and neuronal excitability. FASEB J. ... Another family of membrane proteins that modulate synaptic activity are the voltage gated sodium channels (NAvs). Recently, the ...
... venom peptide ProTx-II with lipid membranes is a prerequisite for its inhibition of human voltage-gated sodium channel NaV1. 7 ... NKA, a member of the tachykinin peptide family, is widely distributed in the mammalian central and peripheral nervous systems. ... In addition, voltage-gated sodium channels play important roles in action potential generation and propagation. Among them, Na ... ProTx II has the potency to inhibit the human voltage-gate sodium channel 1.7 (hNa V1.7), which is involved in nociception and ...
Intro The NaV1.6 isoform from the voltage-gated sodium route was found out in first, and is currently a well-established ... Following an approach previously applied to sodium channel NaV1.5 with significant success(Veeraraghavan, et al., 2018), we ... Further, this type of region was selected predicated on its uniqueness to NaV1.6 (in comparison to other NaV1.x proteins) and ... high amount of conservation across mammalian species. A GREAT TIME search revealed an extremely significant (E = 3 10C7) ...
Heterogeneous expression of voltage-gated potassium channels in the heart: roles in normal excitation and arrhythmias ... Molecular identity of the late sodium current in adult dog cardiomyocytes identified by Nav1. 5 antisense inhibition ... The effects of shortening on myoplasmic calcium concentration and on the action potential in mammalian ventricular muscle ... Na+ channel distribution and electrophysiological heterogeneities in guinea pig ventricular wall. Osadchii, OE; Soltysinska, E ...
... and Nav1.6/SCN8A and shows higher affinity for insect Nav1/para channels (site 3). Induces tonic repetitive firing of nerve ... Selectively slows channel inactivation of mammalian Nav1.1/SCN1A, Nav1.3/SCN3A, ... Ion channel impairing toxin, Neurotoxin, Toxin, Voltage-gated sodium channel impairing toxin. ... Selectively slows channel inactivation of mammalian Nav1.1/SCN1A, Nav1.3/SCN3A, and Nav1.6/SCN8A and shows higher affinity for ...
sodium channel complex. GO:0034706 9.43. SCN2A SCN1B SCN1A 12. voltage-gated sodium channel complex. GO:0001518 9.17. SCN9A ... Modulation of sodium current in mammalian cells by an epilepsy-correlated beta 1-subunit mutation. 61 6 ... voltage-gated sodium channel activity. GO:0005248 9.23. SCN9A SCN8A SCN7A SCN3A SCN2A SCN1B ... Sodium Voltage-Gated Channel Beta Subunit 1. Protein Coding. 800.39. Pathogenic/Likely pathogenic 6 ...
... in which each progeny dendrite started at a narrowed nodal segment expressing voltage gated sodium ion channels at high density ... Nav1.x, Kv1.1), or after migration of DiI in dendrite membranes. Branched afferent terminals formed a laminar radial radiation ... as were nodes at branch points of mammalian muscle afferents. . Hence our results on myelinated afferent nonbinary branching ... and voltage gated ion channels including NaV1.x sodium channels (Fig. 1C3, 1C4) and KV1.1 potassium channels (. not shown. ), ...
Goldin AL Diversity of mammalian voltage-gated sodium channels. Ann. N. Y. Acad. Sci., 1999 Apr 30 , 868 (38-50). ... The type 1 channels (Nav1.x) share significant sequence similarity with each other,4 and all but one have been functionally ... The phylogenetic relationship of mammalian voltage-gated sodium channel alpha subunit genes, including Scn7A can be found at [ ... The glial voltage-gated sodium channel: cell- and tissue-specific mRNA expression. Proc. Natl. Acad. Sci. U.S.A., 1992 Aug 1 , ...
Background The Nav1.7 subtype of voltage-gated sodium channels is specifically expressed in sensory and sympathetic ganglia ... Gene expression analysis showed that that NaV 1.7 was virtually the only tetrodotoxin-sensitive NaV1 gene expressed in guinea ... After undergoing trauma, many non-mammalian organisms, including reptiles, birds, and zebrafish, are capable of regenerating ... Little is known about the neuronal voltage-gated sodium channels (NaVs) that control neurotransmission in the parasympathetic ...
... ion channels expressed in the mammalian brain which includes 145 voltage-gated ion channels of which 40 are voltage-gated ... sodium, potassium, chloride, calcium etc.) and by their gating activity (voltage gating, ligand gating, other forms of gating ... Title: A kinetic map of the homomeric voltage-gated potassium channel (Kv) family Authors: Rajnish Ranjan, Emmanuelle Logette, ... A vast amount of data on Kv channel kinetics is available in the literature. The genes coding for the Kv channels have been ...
TTX resistant voltage-gated sodium channel Nav1. .. 8, responsible for hyperexcitability of nociceptors. , are expressed. ... Touch receptors in mammalian skin cartoon.jpg,thumb,450px, Division of Mechanoreceptors in the Skin]]. ... resistant voltage-gated sodium channel Nav1.8 is expressed as early as embryonic day 17 (E17) in rat. [42] These channels play ... tetrodotoxin (TTX) resistant voltage-gated sodium channel Nav1.8 is expressed as early as embryonic day 17 (E17) in rat. ,ref ...
... that depends upon the voltage-gated Na channel (Nav1. Zudem stoßen Sie bei der körperlichen Untersuchung nicht selten auf ... The proportion of early diagnosed gastric cancers was only 37, Sodium carboxy methyl cellulose E468 Cross-linked sodium carboxy ... C-Jun and a number of Jun family members were isolated from mamma- lian cells based on their abilities to homo- or ... Inactivation of Na channels d. You can choose between popular deposit methods tradiny as Credit Card, Wire Transfer, CashU and ...
2015. Expression and cellular localization of the voltage-gated calcium channel α2δ3 in the rodent retina. Journal of ... 2019. Nav1. 6 promotes inflammation and neuronal degeneration in a mouse model of multiple sclerosis. Journal of ... 100 µl in PBS + 0.03% sodium azide. Adequate amount of material to conduct 10-mini Western Blots. ... Recent findings show that antibodies against RBPMS are robust reagents that exclusively identify RGCs in multiple mammalian ...
... inactivating Nav1.4 voltage-gated sodium channels at the NMJ, and consequently blocking the production of muscle action ... Accumulation of Nav1 mRNAs at differentiating postsynaptic sites in rat soleus muscles * MA Stocksley ... Glial cells decipher synaptic competition at the mammalian neuromuscular junction * H Darabid ... followed by activation of voltage-gated sodium channels (VGSC), leading to action potentials and contraction of muscle (brown ...
... including the voltage-gated sodium channel (Nav1) β2 subunit, Golgi-localized membrane-bound α2,6-sialyltransferase, P-selectin ... Elements of neural adhesion molecules and a yeast vacuolar protein sorting receptor are present in a novel mammalian low ... and had subtle electrophysiological alterations in the steady-state inactivation of their voltage-gated sodium channels. They ... possibly through regulating the potassium ion channel expression, hence affecting neuronal excitability [161]. One study using ...
Regulation of Cardiac Voltage-Gated Sodium Channel by Kinases: Roles of Protein Kinases A and C. Handb Exp Pharmacol. 2017;. * ... Biophysical characterization of the Varroa destructor NaV1 sodium channel and its affinity for τ-fluvalinate insecticide. FASEB ... The making of a mammalian peroxisome, version 2.0: mitochondria get into the mix. Cell Death Differ. 2017;24(7):1148-1152. * ... A leaky voltage sensor domain of cardiac sodium channels causes arrhythmias associated with dilated cardiomyopathy. Sci Rep. ...
  • Gueret, G. 2010-06-02 00:00:00 This study analyzes changes in the distribution, electrophysiological properties, and proteic composition of voltage-gated sodium channels (NaV) in cultured adult rat skeletal muscle fibers. (
  • The action of NSTX produces minimal effect on cardiac Nav, where it exhibits about 20-60 fold lesser affinity than in Nav channels from rat skeletal muscle and rat brain. (
  • Sodium channels in the adult central nervous system and heart contain β 1 through β 4 subunits, whereas sodium channels in adult skeletal muscle have only the β 1 subunit. (
  • Site 3 binds alpha-scorpion and sea anemone toxins, which slow sodium channel inactivation. (
  • By investigating the efficiency of AP propagation over Nav1.8 channels, we find however that the specific inactivation properties of these channels significantly increase the metabolic cost of signaling in C-fibers. (
  • 7 voltage-sensors to inhibit channel activation and inactivation. (
  • Selectively slows channel inactivation of mammalian Nav1.1/SCN1A, Nav1.3/SCN3A, and Nav1.6/SCN8A and shows higher affinity for insect Nav1/para channels (site 3). (
  • NSTX blocks the extracellular portion, the outer vestibule, of some voltage gated sodium channels in a very powerful and reversible manner, without affection of other ion channels. (
  • Sodium-channel proteins in the mammalian brain are composed of an association that include one alpha subunit and one or more auxiliary beta subunits. (
  • Former five, but more recently, six neurotoxin receptor sites have been recognized between the seven receptor site located in the vertebrate sodium channel receptor alpha subunit: Site 1 binds the sodium channel blockers tetrodotoxin and saxitoxin. (
  • The phylogenetic relationship of mammalian voltage-gated sodium channel alpha subunit genes, including Scn7A can be found at [880] . (
  • See figure 1 in Goldin 2000 [878] for a transmembrane folding diagram displaying the structure of a generic voltage gated sodium alpha subunit. (
  • Owing to the well-defined three-dimensional structure and ability to inhibit voltage-gated sodium (Na V ), potassium (K V ) and calcium (Ca V ) ion channels with high potency and selectivity, disulfide-rich peptide toxins have attracted much attention as potential analgesics. (
  • They are classified in terms of which ion passes through the channel (sodium, potassium, chloride, calcium etc.) and by their gating activity (voltage gating, ligand gating, other forms of gating). (
  • There are more than 350 different ion channels expressed in the mammalian brain which includes 145 voltage-gated ion channels of which 40 are voltage-gated potassium (Kv) channels. (
  • Peptide CKRRSETTAETFTE, corresponding to amino acid residues 43-56 of rat β 1 subunit of voltage-gated Na + channels (Accession Q00954 ). (
  • 2-3 Mammalian sodium channels are heterotrimers, composed of a central, pore-forming α subunit and two auxiliary β subunits. (
  • An important gene associated with Generalized Epilepsy with Febrile Seizures Plus is SCN1B (Sodium Voltage-Gated Channel Beta Subunit 1), and among its related pathways/superpathways are Developmental Biology and G-Beta Gamma Signaling . (
  • Such functions include protease inhibitors, membrane pore formation, ion channel blockers and metal binding proteins. (
  • Ion channels (ICs) are proteins that selectively allow ions to diffuse through the cell membrane, creating an electrical potential across the membrane. (
  • Investigators from the University of British Columbia, Great Ormond Street Hospital for Children, and the National Hospital reported their findings on neurotransmitter deficiencies in two patients with mutations in voltage-gated sodium genes (SCN2A and SCN8A) discovered by whole exome sequencing. (
  • Evolution and diversity of mammalian sodium channel genes. (
  • The genes coding for the Kv channels have been cloned and studied in cell lines for many decades. (
  • µ and µO-CTX are two isoforms that specifically target voltage-gated sodium channels. (
  • The mammalian sodium channel isoforms that have been identified thus far can be subdivided into three main groups. (
  • 9-11 Loss, or function mutations in Na V 1.7 channels, leads to complete ablation of pain perception in humans. (
  • Hyperexcitability and mutations of sodium channels are responsible for perception and transmission of inflammatory and neuropathic pain states. (
  • In this study examined a racially and ethnically diverse cohort of IBS patients for SCN5A missense mutations, and compared them to IBS negative controls, and determined the resulting NaV1. (
  • In this review, we describe the current knowledge of µ-CTX interacting with the different sodium channels subtypes, the mechanism of action and their potential therapeutic use as analgesic compounds in the clinical management of pain conditions. (
  • Animal toxins are structurally diverse peptides that are highly potent yet selective on ion channel subtypes and therefore representing valuable probes to elucidate the structures, gating properties and cellular functions of ion channels. (
  • It inhibits multiple sodium channel subtypes but it is reported to be ~100-fold more selective for h Na V 1.7. (
  • Nomenclature of voltage-gated sodium channels. (
  • 1 Na V channels are activated in response to depolarization and selectively allow flow of Na + ions. (
  • Propagation of action potentials (AP) in axons relies on the concerted action of membrane-spanning selectively permeable ion channels ( Hodgkin and Huxley, 1952 ). (
  • ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action potential propagation in nociceptors. (
  • Since then, the Hodgkin-Huxley model has been widely used to build ion channel models and to construct biologically realistic neuron models. (
  • Currently neuron models use generic ion channel currents representing a class of ion channels to capture electrical behavior of neurons. (
  • However, if the neuron was reconstructed with the specific combination of ion channels expressed in the neuron, properly modeling the kinetics of each ion channel type and their distributions, then it would be valid to trace casual events down to specific ion channels. (
  • Moreover, often ion channel kinetics are tweaked to accurately capture neuron electrical behavior resulting in significantly altered ion channel models. (
  • After 4 days of culture, an increase of the NaV1.5 channel type was observed. (
  • These channels exhibited increased activation time constant (τm) and reduced conductance, similar to what has been observed in denervated muscles in vivo, where the density of NaV1.5 was increasing progressively after denervation. (
  • Our data evidenced an increase in NaV1.5 channels and the involvement of β subunits in the regulation of sodium current and fiber excitability. (
  • The SCN5A-encoded voltage-gated mechanosensitive sodium (Na(+)) channel NaV1.5 is expressed in human GI smooth muscle cells and interstitial cells of Cajal. (
  • Voltage-gated sodium channels are established pharmacological targets for local anesthetics and many other drugs with shared mechanisms of action including certain anti-arrhythmic and anti-epilepsy agents. (
  • Site 4 binds beta-scorpion toxins, which affect sodium channel activation. (
  • Toxins such as neosaxitoxin and tetrodotoxin have less affinity for most cardiac Nav channels than for most Nav channels in nerve tissue. (
  • ProTx-II conforms to the inhibitory cystine knot (ICK) 2 motif, a common structural fold among spider toxins targeting ion channels. (
  • The tarantula toxins ProTx-II and HWTX-IV differentially interact with human Nav1. (
  • Nine types of alpha subunits have been described (Nav1.1 to Nav1.9), and a tenth related isoform (Nax) may also play some role as a Nav channel. (
  • At day 7, τh was back to normal and τm still increased, in agreement with a decrease in sodium current and conductance at day 4 and normalization at day 7. (
  • The conceptual transition from conductivity (per surface area) to density of channels, with each channel having only two possible conductance value corresponding to its open and closed states, involves investigating the effects of possible non-uniformities in the distribution of ion channels across the membrane. (
  • In landmark papers of 1952, Hodgkin and Huxley developed a mathematical model of ion conductance to demonstrate the role of ion channels in the electrical behavior of excitable nerve cells. (
  • Thus, like many other neuronal channels and receptors, Nav channels predated neurons. (
  • 11 These recent findings highlight the role of this Na V isoform and the subset of DRG neurons that express this channel in physiological pain sensation. (
  • The number of ion channels on the surface of neurons' membrane is usually thought to be large enough to justify combining the individual channel conductances into a continuous measure of overall conductivity ( Dayan and Abbott, 2001 ), as originally done by Hodgkin and Huxley (1952) . (
  • As the electrical properties of these model neurons faithfully capture those of real neurons, we can trace the causal events of an emergent phenomena down to individual neurons, but we cannot go further down to specific ion channels. (
  • Recent molecular anatomy showed that in C-fibers, the very thin (0.1 μm diameter) axons of the peripheral nervous system, Nav1.8 channels are clustered together on lipid rafts that float in the cell membrane. (
  • Molecular cloning of an atypical voltage-gated sodium channel expressed in human heart and uterus: evidence for a distinct gene family. (
  • Invertebrates possess two Nav channels (Nav1 and Nav2), whereas vertebrate Nav channels are of the Nav1 family. (
  • The glial voltage-gated sodium channel: cell- and tissue-specific mRNA expression. (
  • Genetic disorders that disrupt the function of these channels produce an array of Na(+) channelopathies resulting in neuronal impairment, chronic pain, neuromuscular pathologies, and cardiac arrhythmias. (
  • This chapter outlines sodium channel models with local anesthetics, anticonvulsants, and antiarrhythmics, which are used to manage pain and treat sodium channelopathies. (
  • Local anesthetic receptor site binds local anesthetics, antiarrhythmic drugs and antiepileptic drugs NSTX and other site 1 blockers have high affinity (very low dissociation constant) and high specificity for Nav channels. (
  • The Research Pack contains all you need for Na V 1.7 research: Antibodies recognizing different domains of the channel, a classical Na V channel activator and Na V 1.7 specific blockers, all in one economical package! (
  • Metoprolol and nadolol did not block Na V 1.5 indicating that sodium channel block is not a class effect of β-blockers. (
  • Here, we report a new clinical case of debilitating itch and altered pain perception resulting from the heterozygous de novo p.L811P gain-of-function mutation in Na V 1.9, a voltage-gated sodium (Na V ) channel subtype that relays sensory information from the periphery to the spine. (
  • However, the majority of these models are generic Kv channel models which do not represent the kinetics of gene specific ion channel. (
  • Earlier in vitro electrophysiological studies of the effects of propranolol on heart rate and conduction performed in frog atria, rat and canine ventricular myocytes suggested that the drug might be interacting with sodium channels. (
  • 4-5 The Na V channels are classified into two groups according to their sensitivity to Tetrodotoxin (TTX): TTX-sensitive (Na V 1.1, Na V 1.2, Na V 1.3, Na V 1.4, Na V 1.6 and Na V 1.7) and TTX-resistant (Na V 1.5, Na V 1.8 and Na V 1.9). (
  • We directly tested the effects of propranolol on heterologously expressed recombinant human cardiac (Na V 1.5) and brain (Na V 1.1, Na V 1.2, Na V 1.3) sodium channels using whole-cell patch-clamp recording. (
  • Our findings establish sodium channels as targets for propranolol and may help explain some beneficial effects of the drug in treating cardiac arrhythmias, and may explain certain adverse central nervous system effects. (
  • These, by inducing the entrance of sodium ions in the cell, modulate the neuronal excitability by depolarizing plasma membrane and propagating the action potential. (
  • CK2 is highly expressed in the mammalian brain and has many bona fide substrates that are crucial in neuronal or glial homeostasis and signaling processes across synapses. (
  • Voltage-gated sodium (Na(+)) channels are expressed in virtually all electrically excitable tissues and are essential for muscle contraction and the conduction of impulses within the peripheral and central nervous systems. (
  • Ion channel kinetics are considered among the essential data needed for obtaining a biologically accurate reconstruction of excitable cells. (
  • Pingle SC, Matta JA, Ahern GP (2007) Capsaicin receptor: TRPV1 a promiscuous TRP channel. (
  • Voltage-gated sodium channels (Na V ) are essential for the generation of action potentials and for cell excitability. (
  • hypothesized that action potentials could be propagated along thin ( d ≈ 0.2 μm) axons by "jumping" between individual Na + channels placed a few microns apart. (
  • ProTx II inhibits current by shifting the voltage dependence of activation to more depolarized potentials. (
  • Furthermore, differently from other peptides that may be subjected to poor absorption, proteolysis and biological half-lives, the presence of disulfide bonds confers to CTX a sort of stability based on the cross-linking between the cysteine side chains [ 4 , 5 , 6 ]. (
  • ICK peptides are defined by a 1-4, 2-5, 3-6 cystine connectivity and often have limited regular secondary structure. (
  • Nav channels form the basis for electrical excitability in animals. (
  • Centrifuge all antibody preparations before use (10000 x g 5 min). (
  • Finally, we observed that brain sodium channels exhibited less sensitivity to R-(+)-propranolol than Na V 1.5 channels. (
  • Voltage-gated sodium channels (Navs) play critical roles in action potential generation and propagation. (
  • In addition, voltage-gated sodium channels play important roles in action potential generation and propagation. (
  • Site 2 binds lipid-soluble sodium channel activators such as veratridine. (
  • Therefore, we modeled biophysically realistic unmyelinated axons with both conventional and lipid-raft based organization of Na + channels. (
  • CK2 also phosphorylates and inactivates the lipid phosphatase PTEN which, by dephosphorylating phosphatidylinositol-3,4,5-trisphosphate (PIP3), reverses the activation of the AKT pathway [ 8 ]. (
  • Interaction of tarantula venom peptide ProTx-II with lipid membranes is a prerequisite for its inhibition of human voltage-gated sodium channel NaV1. (
  • Our model is a useful tool to study the effects of denervation in adult muscle fibers in vitro and the expression of sodium channels. (
  • Voltage-gated", also called "voltage-sensitive" and "voltage-dependent" sodium channel also known as "VGSCs" or "Nav channel" are crucial elements of normal physiology in a variety of animals, including flies, leeches, squid and jellyfish, as well as mammalian and non-mammalian vertebrates. (
  • 2010). Recent findings show that antibodies against RBPMS are robust reagents that exclusively identify RGCs in multiple mammalian species (Rodriguez et al. (
  • the ca(2+) channel-targeting spider toxin (cst) family. (
  • ProTx II has the potency to inhibit the human voltage-gate sodium channel 1.7 (hNa V 1.7), which is involved in nociception and might have potential as a pain therapeutic. (
  • [873] None of these channels have been expressed in an exogenous system before 1999, so that it was not possible to draw any conclusions about the properties of these channels before 1999. (
  • Some studies have pointed out that ProTx-II acts by binding to the membrane-embedded voltage sensor domain of h Na V 1.7, but the exact mechanism of action has not been explored clearly. (
  • Because of their importance to the conduction of electrical signals, Na(+) channels are the target of a wide variety of local anesthetic, antiarrhythmic, anticonvulsant, and antidepressant drugs. (
  • In the latter axons the AP jumps along the nodes of Ranvier-discrete, anatomically specialized regions which contain very high densities of sodium ion (Na + ) channels. (
  • thus making the high connection densities of mammalian cortex possible. (
  • Site 5 binds the polyether ladder brevetoxins and ciguatoxin. (
  • Most data emphasize the role of "STX resistant" Nav channel 1.5 in human heart. (
  • The type 2 channels (Nav2.x) are approximately 50% identical to the type 1 channels, with significant differences in regions that are critical for channel function. (
  • Myelinated axons feature a highly structured distribution of voltage-gated ion channels, with a characteristic clustering of Na + channels at the nodes of Ranvier. (
  • Faisal and Laughlin (2007) showed that in order to accurately model thin axons, the behavior of individual ion channels needs to be taken into account. (
  • A vast amount of data on Kv channel kinetics is available in the literature. (
  • The lack of consistency limits the value of these data and prevents a consensus on ion channel kinetics. (