Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.
Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.
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.
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.
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 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)
Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.
Benzoic acid or benzoic acid esters substituted with one or more nitro groups.
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.
Inherited myotonic disorders with early childhood onset MYOTONIA. Muscular hypertrophy is common and myotonia may impair ambulation and other movements. It is classified as Thomsen (autosomal dominant) or Becker (autosomal recessive) generalized myotonia mainly based on the inheritance pattern. Becker type is also clinically more severe. An autosomal dominant variant with milder symptoms and later onset is known as myotonia levior. Mutations in the voltage-dependent skeletal muscle chloride channel are associated with the disorders.
An inhibitor of anion conductance including band 3-mediated anion transport.
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.
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).
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.
The ability of a substrate to allow the passage of ELECTRONS.
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.
An analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis.
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.
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.
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).
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 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.
Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis.
Potassium channels whose activation is dependent on intracellular calcium concentrations.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
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.
A gas that has been used as an aerosol propellant and is the starting material for polyvinyl resins. Toxicity studies have shown various adverse effects, particularly the occurrence of liver neoplasms.
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.
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 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 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 ubiquitous sodium salt that is commonly used to season food.
CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.
The rate dynamics in chemical or physical systems.
A mixture of mostly avermectin H2B1a (RN 71827-03-7) with some avermectin H2B1b (RN 70209-81-3), which are macrolides from STREPTOMYCES avermitilis. It binds glutamate-gated chloride channel to cause increased permeability and hyperpolarization of nerve and muscle cells. It also interacts with other CHLORIDE CHANNELS. It is a broad spectrum antiparasitic that is active against microfilariae of ONCHOCERCA VOLVULUS but not the adult form.
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 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 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.
Solutions that have a lesser osmotic pressure than a reference solution such as blood, plasma, or interstitial fluid.
Established cell cultures that have the potential to propagate indefinitely.
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
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 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.
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 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.
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.
An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.
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.
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 delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.
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.
A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.
Derivatives of ACETIC ACID which contain an hydroxy group attached to the methyl carbon.
A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.
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)
A polyvinyl resin used extensively in the manufacture of plastics, including medical devices, tubing, and other packaging. It is also used as a rubber substitute.
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.
An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.
A group of disorders caused by defective salt reabsorption in the ascending LOOP OF HENLE. It is characterized by severe salt-wasting, HYPOKALEMIA; HYPERCALCIURIA; metabolic ALKALOSIS, and hyper-reninemic HYPERALDOSTERONISM without HYPERTENSION. There are several subtypes including ones due to mutations in the renal specific SODIUM-POTASSIUM-CHLORIDE SYMPORTERS.
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.
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 delayed rectifier subtype of shaker potassium channels that conducts a delayed rectifier current. It contributes to ACTION POTENTIAL repolarization of MYOCYTES in HEART ATRIA.
A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.
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.
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.
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.
Inorganic binary compounds of iodine or the I- ion.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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 quantity of volume or surface area of CELLS.
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 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 voltage-gated potassium channel that is expressed primarily in the HEART.
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.
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.
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.
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.
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.
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 quality of cell membranes which permits the passage of solvents and solutes into and out of cells.
A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.
Mercury chloride (HgCl2). A highly toxic compound that volatizes slightly at ordinary temperature and appreciably at 100 degrees C. It is corrosive to mucous membranes and used as a topical antiseptic and disinfectant.
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 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.
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.
Benzoic acids, salts, or esters that contain an amino group attached to carbon number 2 or 6 of the benzene ring structure.
A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Organic salts or esters of methanesulfonic acid.
A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.
Cell-surface proteins that bind GAMMA-AMINOBUTYRIC ACID with high affinity and trigger changes that influence the behavior of cells. GABA-A receptors control chloride channels formed by the receptor complex itself. They are blocked by bicuculline and usually have modulatory sites sensitive to benzodiazepines and barbiturates. GABA-B receptors act through G-proteins on several effector systems, are insensitive to bicuculline, and have a high affinity for L-baclofen.
A powerful herbicide used as a selective weed killer.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.
Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Proteins prepared by recombinant DNA technology.
A group of compounds with three aromatic rings joined in linear arrangement.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A non-penetrating amino reagent (commonly called SITS) which acts as an inhibitor of anion transport in erythrocytes and other cells.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
The most common inhibitory neurotransmitter in the central nervous system.
Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.
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 cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning.
Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.
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.
Elements of limited time intervals, contributing to particular results or situations.
A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching.
A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.
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.
A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.
Inorganic compounds that contain gold as an integral part of the molecule.
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.
One or more layers of EPITHELIAL CELLS, supported by the basal lamina, which covers the inner or outer surfaces of the body.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.
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 strain of mice widely studied as a model for cystic fibrosis. These mice are generated from embryonic stem cells in which the CFTR (cystic fibrosis transmembrane conductance regulator) gene is inactivated by gene targeting. As a result, all mice have one copy of this altered gene in all their tissues. Mice homozygous for the disrupted gene exhibit many features common to young cystic fibrosis patients, including failure to thrive, meconium ileus, and alteration of mucous and serous glands.
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.
CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.
A chlorinated hydrocarbon that has been used as an inhalation anesthetic and acts as a narcotic in high concentrations. Its primary use is as a solvent in manufacturing and food technology.
A genus of the Torpedinidae family consisting of several species. Members of this family have powerful electric organs and are commonly called electric rays.
The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent.
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.
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)
An acidifying agent that has expectorant and diuretic effects. Also used in etching and batteries and as a flux in electroplating.
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 subclass of ion channels that open or close in response to the binding of specific LIGANDS.
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 strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A species of the true toads, Bufonidae, widely distributed in the United States and Europe.
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.
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.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.
A salt of lithium that has been used experimentally as an immunomodulator.
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 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.
An alkaloid found in the seeds of STRYCHNOS NUX-VOMICA. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison.
Membrane proteins whose primary function is to facilitate the transport of negatively charged molecules (anions) across a biological membrane.
Salts of hydrobromic acid, HBr, with the bromine atom in the 1- oxidation state. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
CALCIUM CHANNELS located in the neurons of the brain.
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 non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.
The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
A noncompetitive antagonist at GABA-A receptors and thus a convulsant. Picrotoxin blocks the GAMMA-AMINOBUTYRIC ACID-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates.
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 condition characterized by calcification of the renal tissue itself. It is usually seen in distal RENAL TUBULAR ACIDOSIS with calcium deposition in the DISTAL KIDNEY TUBULES and the surrounding interstitium. Nephrocalcinosis causes RENAL INSUFFICIENCY.
CALCIUM CHANNELS located in the neurons of the brain. They are inhibited by the marine snail toxin, omega conotoxin MVIIC.
The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.
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.
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.
A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
Substances used in the treatment or control of nematode infestations. They are used also in veterinary practice.
A subclass of symporters that specifically transport SODIUM CHLORIDE and/or POTASSIUM CHLORIDE across cellular membranes in a tightly coupled process.
Use of electric potential or currents to elicit biological responses.
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.
Inorganic compounds that contain barium as an integral part of the molecule.
A mixture of alkylbenzyldimethylammonium compounds. It is a bactericidal quaternary ammonium detergent used topically in medicaments, deodorants, mouthwashes, as a surgical antiseptic, and as a as preservative and emulsifier in drugs and cosmetics.
A variety of neuromuscular conditions resulting from MUTATIONS in ION CHANNELS manifesting as episodes of EPILEPSY; HEADACHE DISORDERS; and DYSKINESIAS.
A cadmium halide in the form of colorless crystals, soluble in water, methanol, and ethanol. It is used in photography, in dyeing, and calico printing, and as a solution to precipitate sulfides. (McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.
The physical characteristics and processes of biological systems.
A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.
A family of membrane proteins that selectively conduct SODIUM ions due to changes in the TRANSMEMBRANE POTENTIAL DIFFERENCE. They typically have a multimeric structure with a core alpha subunit that defines the sodium channel subtype and several beta subunits that modulate sodium channel activity.
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 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.
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.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.
A sulfamyl diuretic.
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.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
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.
A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.
A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.
Na-K-Cl transporter ubiquitously expressed. It plays a key role in salt secretion in epithelial cells and cell volume regulation in nonepithelial cells.
Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.
The balance of fluid in the BODY FLUID COMPARTMENTS; total BODY WATER; BLOOD VOLUME; EXTRACELLULAR SPACE; INTRACELLULAR SPACE, maintained by processes in the body that regulate the intake and excretion of WATER and ELECTROLYTES, particularly SODIUM and POTASSIUM.
An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to CADMIUM POISONING.
The nonstriated involuntary muscle tissue of blood vessels.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
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)
A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.
A potent vasodilator agent that increases peripheral blood flow.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
Cell surface proteins that bind biogenic amines with high affinity and regulate intracellular signals which influence the behavior of cells. Biogenic amine is a chemically imprecise term which, by convention, includes the catecholamines epinephrine, norepinephrine, and dopamine, the indoleamine serotonin, the imidazolamine histamine, and compounds closely related to each of these.
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.

Relaxation of endothelin-1-induced pulmonary arterial constriction by niflumic acid and NPPB: mechanism(s) independent of chloride channel block. (1/2847)

We investigated the effects of the Cl- channel blockers niflumic acid, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and 4, 4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) on endothelin-1 (ET-1)-induced constriction of rat small pulmonary arteries (diameter 100-400 microm) in vitro, following endothelium removal. ET-1 (30 nM) induced a sustained constriction of rat pulmonary arteries in physiological salt solution. Arteries preconstricted with ET-1 were relaxed by niflumic acid (IC50: 35.8 microM) and NPPB (IC50: 21.1 microM) in a reversible and concentration-dependent manner. However, at concentrations known to block Ca++-activated Cl- channels, DIDS (+info)

Chloride dependence of hyperpolarization-activated chloride channel gates. (2/2847)

1. ClC proteins are a class of voltage-dependent Cl- channels with several members mutated in human diseases. The prototype ClC-0 Torpedo channel is a dimeric protein; each subunit forms a pore that can gate independently from the other one. A common slower gating mechanism acts on both pores simultaneously; slow gating activates ClC-0 at hyperpolarized voltages. The ClC-2 Cl- channel is also activated by hyperpolarization, as are some ClC-1 mutants (e.g. D136G) and wild-type (WT) ClC-1 at certain pH values. 2. We studied the dependence on internal Cl- ([Cl-]i) of the hyperpolarization-activated gates of several ClC channels (WT ClC-0, ClC-0 mutant P522G, ClC-1 mutant D136G and an N-terminal deletion mutant of ClC-2), by patch clamping channels expressed in Xenopus oocytes. 3. With all these channels, reducing [Cl-]i shifted activation to more negative voltages and reduced the maximal activation at most negative voltages. 4. We also investigated the external halide dependence of WT ClC-2 using two-electrode voltage-clamp recording. Reducing external Cl- ([Cl-]o) activated ClC-2 currents. Replacing [Cl-]o by the less permeant Br- reduced channel activity and accelerated deactivation. 5. Gating of the ClC-2 mutant K566Q in normal [Cl-]o resembled that of WT ClC-2 in low [Cl-]o, i.e. channels had a considerable open probability (Po) at resting membrane potential. Substituting external Cl- by Br- or I- led to a decrease in Po. 6. The [Cl-]i dependence of the hyperpolarization-activated gates of various ClC channels suggests a similar gating mechanism, and raises the possibility that the gating charge for the hyperpolarization-activated gate is provided by Cl-. 7. The external halide dependence of hyperpolarization-activated gating of ClC-2 suggests that it is mediated or modulated by anions as in other ClC channels. In contrast to the depolarization-activated fast gates of ClC-0 and ClC-1, the absence of Cl- favours channel opening. Lysine 556 may be important for the relevant binding site.  (+info)

Volume regulation following hypotonic shock in isolated crypts of mouse distal colon. (3/2847)

1. A video-imaging technique of morphometry was used to measure the diameter as an index of cell volume in intact mouse distal colon crypts submitted to hypotonic shock. 2. Transition from isotonic (310 mosmol l-1) to hypotonic (240 mosmol l-1) saline caused a pronounced increase in crypt diameter immediately followed by regulatory volume decrease (RVD). 3. Exposure of crypts to Cl--free hyposmotic medium increased the rapidity of both cell swelling and RVD. Exposure of crypts to Na+-free hyposmotic medium reduced the total duration of swelling. Return to initial diameter was followed by further shrinkage of the crypt cells. 4. The chloride channel inhibitor NPPB (50 microM) delayed the swelling phase and prevented the subsequent normal decrease in diameter. 5. The K+ channel blockers barium (10 mM), charybdotoxin (10 nM) and TEA (5 mM) inhibited RVD by 51, 44 and 32 %, respectively. 6. Intracellular [Ca2+] rose from a baseline of 174 +/- 17 nM (n = 8) to 448 +/- 45 nM (n = 8) during the initial swelling phase 7. The Ca2+ channel blockers verapamil (50 microM) and nifedipine (10 microM), the chelator of intracellular Ca2+ BAPTA AM (30 microM), or the inhibitor of Ca2+ release TMB-8 (10 microM), dramatically reduced volume recovery, leading to 51 % (n = 9), 25 % (n = 7), 37 % (n = 6), 32 % (n = 8) inhibition of RVD, respectively. TFP (50 microM), an antagonist of the Ca2+-calmodulin complex, significantly slowed RVD. The Ca2+ ionophore A23187 (2 microM) provoked a dramatic reduction of the duration and amplitude of cell swelling followed by extensive shrinkage. The release of Ca2+ from intracellular stores using bradykinin (1 microM) or blockade of reabsorption with thapsigargin (1 microM) decreased the duration of RVD. 8. Prostaglandin E2 (PGE2, 5 microM) slightly delayed RVD, whereas leukotriene D4 (LTD4, 100 nM) and arachidonic acid (10 microM) reduced the duration of RVD. Blockade of phospholipase A2 by quinacrine (10 microM) inhibited RVD by 53 %. Common inhibition of PGE2 and LTD4 synthesis by ETYA (50 microM) or separate blockade of PGE2 synthesis by 1 microM indomethacin reduced the duration of RVD. Blockade of LTD4 synthesis by nordihydroguaiaretic acid (NDGA) did not produce any significant effect on cell swelling or subsequent RVD. 9. Staurosporine (1 microM), an inhibitor of protein kinases, inhibited RVD by 58 %. Taken together the experiments demonstrate that the RVD process is under the control of conductive pathways, extra- and intracellular Ca2+ ions, protein kinases, prostaglandins and leukotrienes.  (+info)

Acetylcholine-induced membrane potential changes in endothelial cells of rabbit aortic valve. (4/2847)

1. Using a microelectrode technique, acetylcholine (ACh)-induced membrane potential changes were characterized using various types of inhibitors of K+ and Cl- channels in rabbit aortic valve endothelial cells (RAVEC). 2. ACh produced transient then sustained membrane hyperpolarizations. Withdrawal of ACh evoked a transient depolarization. 3. High K+ blocked and low K+ potentiated the two ACh-induced hyperpolarizations. Charybdotoxin (ChTX) attenuated the ACh-induced transient and sustained hyperpolarizations; apamin inhibited only the sustained hyperpolarization. In the combined presence of ChTX and apamin, ACh produced a depolarization. 4. In Ca2+-free solution or in the presence of Co2+ or Ni2+, ACh produced a transient hyperpolarization followed by a depolarization. In BAPTA-AM-treated cells, ACh produced only a depolarization. 5. A low concentration of A23187 attenuated the ACh-induced transient, but not the sustained, hyperpolarization. In the presence of cyclopiazonic acid, the hyperpolarization induced by ACh was maintained after ACh removal; this maintained hyperpolarization was blocked by Co2+. 6. Both NPPB and hypertonic solution inhibited the membrane depolarization seen after ACh washout. Bumetanide also attenuated this depolarization. 7. It is concluded that in RAVEC, ACh produces a two-component hyperpolarization followed by a depolarization. It is suggested that ACh-induced Ca2+ release from the storage sites causes a transient hyperpolarization due to activation of ChTX-sensitive K+ channels and that ACh-activated Ca2+ influx causes a sustained hyperpolarization by activating both ChTX- and apamin-sensitive K+ channels. Both volume-sensitive Cl- channels and the Na+-K+-Cl- cotransporter probably contribute to the ACh-induced depolarization.  (+info)

ATP dependence of the ICl,swell channel varies with rate of cell swelling. Evidence for two modes of channel activation. (5/2847)

Swelling-induced activation of the outwardly rectifying anion current, ICl, swell, is modulated by intracellular ATP. The mechanisms by which ATP controls channel activation, however, are unknown. Whole cell patch clamp was employed to begin addressing this issue. Endogenous ATP production was inhibited by dialyzing N1E115 neuroblastoma cells for 4-5 min with solutions containing (microM): 40 oligomycin, 5 iodoacetate, and 20 rotenone. The effect of ATP on current activation was observed in the absence of intracellular Mg2+, in cells exposed to extracellular metabolic inhibitors for 25-35 min followed by intracellular dialysis with oligomycin, iodoacetate, and rotenone, after substitution of ATP with the nonhydrolyzable analogue AMP-PNP, and in the presence of AMP-PNP and alkaline phosphatase to dephosphorylate intracellular proteins. These results demonstrate that the ATP dependence of the channel requires ATP binding rather than hydrolysis and/or phosphorylation reactions. When cells were swollen at 15-55%/min in the absence of intracellular ATP, current activation was slow (0.3-0.8 pA/pF per min). ATP concentration increased the rate of current activation up to maximal values of 4-6 pA/pF per min, but had no effect on the sensitivity of the channel to cell swelling. Rate of current activation was a saturable, hyperbolic function of ATP concentration. The EC50 for ATP varied inversely with the rate of cell swelling. Activation of current was rapid (4-6 pA/pF per min) in the absence of ATP when cells were swollen at rates >/=65%/min. Intracellular ATP concentration had no effect on current activation induced by high rates of swelling. Current activation was transient when endogenous ATP was dialyzed out of the cytoplasm of cells swollen at 15%/min. Rundown of the current was reversed by increasing the rate of swelling to 65%/min. These results indicate that the channel and/or associated regulatory proteins are capable of sensing the rate of cell volume increase. We suggest that channel activation occurs via ATP-dependent and -independent mechanisms. Increasing the rate of cell swelling appears to increase the proportion of channels activating via the ATP-independent pathway. These findings have important physiological implications for understanding ICl, swell regulation, the mechanisms by which cells sense volume changes, and volume homeostasis under conditions where cell metabolism is compromised.  (+info)

The muscle chloride channel ClC-1 has a double-barreled appearance that is differentially affected in dominant and recessive myotonia. (6/2847)

Single-channel recordings of the currents mediated by the muscle Cl- channel, ClC-1, expressed in Xenopus oocytes, provide the first direct evidence that this channel has two equidistant open conductance levels like the Torpedo ClC-0 prototype. As for the case of ClC-0, the probabilities and dwell times of the closed and conducting states are consistent with the presence of two independently gated pathways with approximately 1.2 pS conductance enabled in parallel via a common gate. However, the voltage dependence of the common gate is different and the kinetics are much faster than for ClC-0. Estimates of single-channel parameters from the analysis of macroscopic current fluctuations agree with those from single-channel recordings. Fluctuation analysis was used to characterize changes in the apparent double-gate behavior of the ClC-1 mutations I290M and I556N causing, respectively, a dominant and a recessive form of myotonia. We find that both mutations reduce about equally the open probability of single protopores and that mutation I290M yields a stronger reduction of the common gate open probability than mutation I556N. Our results suggest that the mammalian ClC-homologues have the same structure and mechanism proposed for the Torpedo channel ClC-0. Differential effects on the two gates that appear to modulate the activation of ClC-1 channels may be important determinants for the different patterns of inheritance of dominant and recessive ClC-1 mutations.  (+info)

A single hydrophobic residue confers barbiturate sensitivity to gamma-aminobutyric acid type C receptor. (7/2847)

Barbiturate sensitivity was imparted to the human rho1 homooligomeric gamma-aminobutyric acid (GABA) receptor channel by mutation of a tryptophan residue at position 328 (Trp328), which is located within the third transmembrane domain. Substitutions of Trp328 with a spectrum of amino acids revealed that nearly all hydrophobic residues produced receptor channels that were both directly activated and modulated by pentobarbital with similar sensitivities. Previous studies with ligand-gated ion channels (including GABA) have demonstrated that even conservative amino acid substitution within the agonist-dependent activation domain (N-terminal extracellular domain) can markedly impair agonist sensitivity. Thus, the lack of significant variation in pentobarbital sensitivity among the Trp328 mutants attests to an intrinsic difference between pentobarbital- and the GABA-dependent activation domain. Compared with the heterooligomeric alphabetagamma receptor channel, the mode of modulation for homooligomeric Trp328 mutants by pentobarbital was more dependent on the GABA concentration, yielding potentiation only at low concentrations of GABA (fractions of their respective EC50 values), yet causing inhibition at higher concentrations. Agonist-related studies have also demonstrated that residue 328 plays an important role in agonist-dependent activation, suggesting a functional interconnection between the GABA and pentobarbital activation domains.  (+info)

Functional and molecular characterization of a volume-sensitive chloride current in rat brain endothelial cells. (8/2847)

1. Volume-activated chloride currents in cultured rat brain endothelial cells were investigated on a functional level using the whole-cell voltage-clamp technique and on a molecular level using the reverse transcriptase-polymerase chain reaction (RT-PCR). 2. Exposure to a hypotonic solution caused the activation of a large, outward rectifying current, which exhibited a slight time-dependent decrease at strong depolarizing potentials. The anion permeability of the induced current was I- (1.7) > Br- (1.2) > Cl- (1.0) > F- (0. 7) > gluconate (0.18). 3. The chloride channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB, 100 microM) rapidly and reversibly inhibited both inward and outward currents. The chloride transport blocker 4,4'-diisothiocyanatostilbene-2, 2'-disulphonic acid (DIDS, 100 microM) also blocked the hypotonicity-induced current in a reversible manner. In this case, the outward current was more effectively suppressed than the inward current. The volume-activated current was also inhibited by the antioestrogen tamoxifen (10 microM). 4. The current was dependent on intracellular ATP and independent of intracellular Ca2+. 5. Activation of protein kinase C by phorbol 12,13-dibutyrate (PDBu, 100 nM) inhibited the increase in current normally observed following hypotonic challenge. 6. Extracellular ATP (10 mM) inhibited the current with a more pronounced effect on the outward than the inward current. 7. Verapamil (100 microM) decreased both the inward and the outward hypotonicity-activated chloride current. 8. RT-PCR analysis was used to determine possible molecular candidates for the volume-sensitive current. Expression of the ClC-2, ClC-3 and ClC-5 chloride channels, as well as pICln, could be shown at the mRNA level. 9. We conclude that rat brain endothelial cells express chloride channels which are activated by osmotic swelling. The biophysical and pharmacological properties of the current show strong similarities to those of ClC-3 channel currents as described in other cell types.  (+info)

CLIC4 (chloride intracellular channel 4), Authors: Velayuthan C Padmakumar, Stuart H Yuspa. Published in: Atlas Genet Cytogenet Oncol Haematol.
AbstractBackground and Aim:Our previous proteomic research found that chloride intracellular channel 1 (CLIC1) was upregulated in hepatocellular carcinoma (HCC) tissues with portal vein tumor thrombus. The present study aimed to determine the role of CLIC1 in HCC invasion.Methods:Immunohistochemistr
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Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration in vivo is much higher than other anions. Several families of voltage-gated channels and ligand-gated channels (e.g., the CaCC families) have been characterized in humans. Voltage-gated chloride channels display a variety of important physiological and cellular roles that include regulation of pH, volume homeostasis, organic solute transport, cell migration, cell proliferation and differentiation. Based on sequence homology the chloride channels can be subdivided into a number of groups. Voltage-gated chloride channels are important for setting cell resting membrane potential and maintaining proper cell volume. These channels conduct Cl− as well as other anions such as HCO− 3, I−, SCN−, and NO− 3. The structure of these channels are not like other known channels. The chloride channel subunits ...
0017] Also provided herein is a method of identifying an agent that is an inhibitor of a calcium-activated chloride channel comprising: (a) contacting a cell and a candidate agent in a test sample, (under conditions and for a time sufficient) to permit interaction between the candidate agent and the cell, wherein the cell comprises (i) a calcium-activated chloride channel and (ii) a cytoplasmic indicator protein that binds halide; (b) adding to the test sample (i) at least one calcium-elevating agonist and (ii) iodide, under conditions and for a time sufficient for the calcium-elevating agonist to bind to the cell (i.e., to permit binding of the calcium-elevating agonist to the cell), wherein binding of the calcium-elevating agonist to the cell increases the level of calcium ion (Ca2+) in the cell; and (c) determining the level of iodide influx in the presence of the candidate agent and comparing the level of iodide influx in the presence of the candidate agent with the level of iodide influx in ...
TY - JOUR. T1 - Ca2+- and volume-sensitive chloride currents are differentially regulated by agonists and store-operated Ca2+ entry.. AU - Zholos, Alexander. AU - Prevarskaya, N.. AU - Beck, B.. AU - Sydorenko, V.. AU - Lemonnier, L.. AU - Bordat, P.. AU - Skryma, R.. PY - 2005/2. Y1 - 2005/2. N2 - Using patch-clamp and calcium imaging techniques, we characterized the effects of ATP and histamine on human keratinocytes. In the HaCaT cell line, both receptor agonists induced a transient elevation of [Ca2+]i in a Ca2+-free medium followed by a secondary [Ca2+]i rise upon Ca2+ readmission due to store-operated calcium entry (SOCE). In voltage-clamped cells, agonists activated two kinetically distinct currents, which showed differing voltage dependences and were identified as Ca2+-activated (ICl(Ca)) and volume-regulated (ICl, swell) chloride currents. NPPB and DIDS more efficiently inhibited ICl(Ca) and ICl, swell, respectively. Cell swelling caused by hypotonic solution invariably activated ICl, ...
Two new calcium-activated chloride channel (CLCA) family members, mCLCA5 and mCLCA6, have been cloned from mouse eye and intestine, respectively. mCLCA5 is highly homologous to hCLCA2, and mCLCA6 is highly homologous to hCLCA4. mCLCA5 is widely expressed with strong expression in eye and spleen, whe …
Protein tyrosine kinase and protein phosphatase signaling pathways regulate volume-sensitive chloride currents in a nonpigmented ciliary epithelial cell line.
RefSeq Summary (NM_001288): Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. Chloride intracellular channel 1 is a member of the p64 family; the protein localizes principally to the cell nucleus and exhibits both nuclear and plasma membrane chloride ion channel activity. [provided by RefSeq, Jul 2008 ...
Read Permeant Anions Control Gating of Calcium-dependent Chloride Channels, The Journal of Membrane Biology on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
Chloride intracellular channels (CLICs) are a family of unique proteins, that were suggested to adopt both soluble and membrane-associated forms. Moreover, following this unusual metamorphic change, CLICs were shown to incorporate into membranes and mediate ion conduction in vitro, suggesting multimerization upon membrane insertion. Here, we present a 1.8 Å resolution crystal structure of the CLIC domain of mouse CLIC6 (mCLIC6). The structure reveals a monomeric arrangement and shows a high degree of structural conservation with other CLICs. Small-angle X-ray scattering (SAXS) analysis of mCLIC6 demonstrated that the overall solution structure is similar to the crystallographic conformation. Strikingly, further analysis of the SAXS data using ensemble optimization method unveiled additional elongated conformations, elucidating high structural plasticity as an inherent property of the protein. Moreover, structure-guided perturbation of the inter-domain interface by mutagenesis resulted in a population
CLIC1 antibody, N-term (chloride intracellular channel 1) for IHC-P, WB. Anti-CLIC1 pAb (GTX48722) is tested in Human, Mouse samples. 100% Ab-Assurance.
The ClC chloride channels catalyse the selective flow of Cl- ions across cell membranes, thereby regulating electrical excitation in skeletal muscle and the flow of salt and water across epithelial barriers. Genetic defects in ClC Cl- channels underlie several familial muscle and kidney diseases. He …
Anoctamins and Bestrophins are two kinds of calcium-activated chloride channels. Anoctamins were shown to be Ca-activated Cl channels in 2008 and are responsible for the classical CaCCs that are widely expressed in many tissues, especially epithelia. Bestrophins are more restricted in their expression and play more specialized roles. Bestrophin-1 is expressed in the retinal pigment epithelium and certain mutations in bestrophin-1 cause degeneration of the retina and blindness. Bestrophin-2 is expressed in goblet cells in colon and may play a role in bicarbonate secretion in this tissue. We are interested in understanding how both anoctamins and bestrophins are regulated by calcium. We are identifying the calcium binding sites and the molecular links between the calcium sensor and the channel gate using a combination of both whole-cell and single channel electrophysiological mesurements and mutagenesis. We are dissecting the signaling protein network associated with these channels using ...
Plasma membrane Cl- channels perform a variety of functions, including control of excitability in neurons and muscle, cell volume regulation and transepithelial transport. Structurally, three classes of Cl- channels have been identified: ligand-gated, postsynaptic Cl- channels (e.g. GABA and glycine receptors); the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels (which belong to the traffic ATPase superfamily); and the CLC family of Cl- channels. Recent developments of note include further characterization of the expanding CLC Cl- channel family, advances in understanding the regulation of the CFTR Cl- channel and its emergent role as a regulator of other channels, clarification of issues related to swelling-activated Cl- channels, and the discovery that several co-transporter molecules are now known to induce Cl- currents in Xenopus oocytes.. ...
Proteins encoded by best1 to -3 genes are implicated as molecular correlates of calcium-activated chloride channels in epithelia. In this issue of Circulation Research, Matchkov et al present compelling evidence that best-3 expression is essential for the generation of calcium-sensitive cGMP-dependent chloride channels in rat mesenteric artery.1. Chloride channels are enigmatic beasts. Numerous phenotypes exist, as determined by their mode of activation, channel kinetics, and pore properties, but the molecular identity has only really been identified for the voltage-dependent Cl− channels (CLCs) and the cAMP-dependent, cystic fibrosis transmembrane regulator (CFTR) channels. For the other types of Cl− channels, there is far less certainty about the molecular identity. Many candidates for the swelling-activated Cl− channel have been promulgated that ultimately have been repudiated.2 Similarly, the molecular identity of the Ca2+-gated Cl− channel, common to vascular smooth muscle cells, ...
May be involved in mediating calcium-activated chloride conductance (PubMed:8537359). May play critical roles in goblet cell metaplasia, mucus hypersecretion, cystic fibrosis and AHR. May be involved in the regulation of mucus production and/or secretion by goblet cells. Involved in the regulation of tissue inflammation in the innate immune response. May play a role as a tumor suppressor. Induces MUC5AC.
High blood pressure is the leading risk factor for death worldwide. One of the hallmarks is a rise of peripheral vascular resistance, which largely depends on arteriole tone. Ca2+-activated chloride currents (CaCCs) in vascular smooth muscle cells (VSMCs) are candidates for increasing vascular contractility. We analyzed the vascular tree and identified substantial CaCCs in VSMCs of the aorta and carotid arteries. CaCCs were small or absent in VSMCs of medium-sized vessels such as mesenteric arteries and larger retinal arterioles. In small vessels of the retina, brain, and skeletal muscle, where contractile intermediate cells or pericytes gradually replace VSMCs, CaCCs were particularly large. Targeted disruption of the calcium-activated chloride channel TMEM16A, also known as ANO1, in VSMCs, intermediate cells, and pericytes eliminated CaCCs in all vessels studied. Mice lacking vascular TMEM16A had lower systemic blood pressure and a decreased hypertensive response following vasoconstrictor ...
TY - JOUR. T1 - Characterization of a native swelling-induced chloride current, ICl.swell, and its regulatory protein, pICln, in Xenopus oocytes.. AU - Ackerman, Michael John. AU - Krapivinsky, G. B.. AU - Gordon, E.. AU - Krapivinsky, L.. AU - Clapham, D. C.. PY - 1994. Y1 - 1994. N2 - The ability to precisely regulate cell volume is a fundamental property of most cells. Although the phenomenon of regulatory volume decrease (RVD), whereby a swollen cell loses salt and water to restore its original volume, has been appreciated for decades, the molecular identities of the proteins responsible for the volume control machinery and their regulation are essentially unknown. It appears that the rate-determining step in gaining volume control involves the activation of potassium and chloride conductance pathways. We have identified a native chloride current (ICl.swell) responsive to cell swelling in Xenopus oocytes [Ackerman et al. (1994) J Gen Physiol 103: 153-179]. Moreover, we have demonstrated that ...
The transmembrane protein TMEM16A forms a Ca2+-activated Cl− channel that is permeable to many anions, including SCN−, I−, Br−, Cl−, and HCO3−, and has been implicated in various physiological functions. Indeed, controlling anion permeation through the TMEM16A channel pore may be critical in
Chloride-conducting ion channels of the ClC family are emerging as critical contributors to a host of biological processes. These polytopic membrane proteins form aqueous pathways through which anions are selectively allowed to pass down their concentration gradients. The ClCs are found in nearly all organisms, with members in every mammalian tissue, yet relatively little is known about their mechanism or regulation. It is clear, however, that they are fundamentally different in molecular construction and mechanism from the well-known potassium-, sodium-, and calcium-selective channels. The medical importance of ClC channels - four inherited diseases have been blamed on familial ClC dysfunction to date - highlights their diverse physiological functions and provides strong motivation for further study.
The CLC family of chloride channels and transporters is made up by nine members but just three of these ClC-Ka/b ClC-7 and ClC-2 have already been found up to now connected with auxiliary subunits. immunoglobulin (Ig)-like domains regulates its subcellular localization and activity in glial cells. The normal theme for these three proteins can be their requirement of an effective homeostasis since their breakdown leads to specific illnesses. We will review right here their properties and their part in regular chloride physiology as well as the pathological outcomes of their incorrect function. Intro Chloride is very important to many biological features such Apremilast as for example transepithelial fluid transportation acidification of intracellular organelles muscle tissue contraction neuronal membrane potential or cell quantity rules. Chloride flux across membranes is mediated by several classes of proteins (Duran oocytes or in transfected cells (Steinmeyer gene lead to classical Bartter ...
Miller, A. N.*, Vaisey, G.*, & Long, S. B. (2019). Molecular mechanisms of gating in the calcium-activated chloride channel bestrophin. eLife (Abstract , open state Cryo-EM map , Atomic Coordinates). *A. N. Miller and G. Vaisey are co-first authors.. Vaisey, G., & Long, S. B. (2018). An allosteric mechanism of inactivation in the calcium-dependent chloride channel BEST1. The Journal of General Physiology, jgp.201812190. (Abstract). Hou, X., Burstein, S. R., & Long, S. B. (2018). Structures reveal opening of the store-operated calcium channel Orai. eLife, 7. (Manuscript , Atomic Coordinates). Baradaran, R., Wang, C., Siliciano, A. F., & Long, S. B. (2018). Cryo-EM structures of fungal and metazoan mitochondrial calcium uniporters. Nature, 559(7715), 580-584. (Abstract , Atomic Coordinates , Cryo-EM map). Melinda Diver, Leanne Pedi, Akiko Koide, Shohei Koide, Stephen B. Long (2018). Atomic structure of the eukaryotic intramembrane RAS methyltransferase ICMT. Nature. Jan 25; 553(7689):526-529. ...
The CLC family comprises a group of integral membrane proteins that translocate Cl− across the cell membranes; members of this family are essential for the maintenance of membrane potential, regulation of transepithelial Cl− transport, and control of intravesicular pH (1-3). Human CLC proteins can be divided into two subtypes. The first subtype consists of Cl− channels: CLC-1, CLC-2, CLC-Ka, and CLC-Kb, which are mainly found at the cell membrane, where they function to control the Cl− flow and to stabilize the membrane potential (4). The remaining CLC proteins (CLC-3 to CLC-7) are electrogenic Cl−/H+ antiporters (5-8) that exchange Cl− and H+ with a stoichiometry of 2:1. CLC proteins function as dimers, with each subunit having its own passageway for ion transport (9-15). Previous macroscopic current and single-channel studies have indicated that CLC proteins apparently display two distinct types of gating process (9, 16, 17): fast gating (protopore gate), wherein the ...
Furthermore, the inhibitor pharmacology of the VACC also confirms that they are VACCs. Conventional chloride channel blockers such as NPPB and DIDS significantly inhibited the volume-activated currents, indicating that they are chloride channels (21). In various cell types, DIDS has been shown to inhibit VACCs in voltage-dependent fashion (26, 32, 33) in addition to inhibiting calcium-activated chloride channels (1, 3), outwardly rectifying chloride channels (5), and ATP release (5) but does not inhibit CFTR (1, 10). Thus the voltage-dependent inhibition of volume-activated current by DIDS implies that chloride conductance via CFTR may not play a major role in RVD in cholangiocytes, and this conclusion is consistent with the previous finding that cAMP agonists had no significant effect on RVD in cholangiocytes (6). The VACCs are also inhibited by glybenclamide (Fig. 5C), which is a known inhibitor of CFTR, VACCs, as well as ATP-sensitive potassium channels (27). Moreover, the significant ...
Superfusion of BC3H1 cells with the normal hyposmotic solution caused cell swelling accompanied by a large increase in membrane currents in all the tested cells (Fig. 1 A). Membrane currents returned to basal level after switching back to isosmotic solution (Voets et al., 1997). Current-voltage relations reconstructed from voltage ramps applied during the hyposmotic challenge (Fig. 1 B) show that the swelling-activated current reverses close to ECl (−20 mV). We have previously shown that this current is a Cl− current, ICl,swell, with an I− , Br− , Cl− ,, gluconate anion permeability sequence and that it is efficiently blocked by niflumic acid, flufenamic acid, and NPPB (Voets et al., 1997). This current inactivates during voltage steps to positive potentials ,+40 mV (Fig. 1 C). The negative slope of the current-voltage relation seen at very positive potentials (Fig. 1 B) is due to inactivation of the current during the slow voltage ramp.. We observed single-channel Cl− currents in ...
Ion channels catalyze the transportation of small ions across the cell membrane and, in doing so, maintain normal cellular functions. To achieve functional flexibility, these membrane proteins are regulated by a variety of factors, such as transmembrane voltages, mechanical stretches, extracellular or intracellular ligands, and sometimes the small ions in the aqueous solution (Hille 1992). In vertebrate skeletal muscles, for instance, external Cl− and H+ significantly influence the resting membrane conductance and, thus, control the firing pattern of action potentials (Hodgkin and Horowicz 1959, Hodgkin and Horowicz 1960). Electrophysiological recordings and flux assays have shown that the muscle membrane is more permeable to Cl− than to K+ (Hodgkin and Horowicz 1959; Hutter and Padsha 1959; Hutter and Noble 1960), and if the Cl− conductance is removed, the membrane current shows little change when the pH is altered (Hutter and Warner 1967, Hutter and Warner 1972). These early studies ...
Abstract Inositol 1,4,5-triphosphate receptors (IP3R) are tetrameric intracellular channels that mediate the release of Calcium (Ca2+) from sarcoplasmic reticulum (SR) into the cytosol in response to IP3 binding. Modulation of vascular smooth muscle cells (VSMC) contractility allows small arteries to regulate blood flow and determine peripheral vascular resistance and blood pressure levels. The level of contraction of VSMC relies on a rise in cytoplasmic Ca2+ mediated by IP3-dependent Ca2+ release and voltage dependent Ca2+ influx through L-type Ca2+ (CaL) channels. Strong evidence supports a role for the vascular CaL channels in hypertension but little is known about the functional role of IP3R including the modulation of IP3R-Ca2+ signaling by the vascular endothelium. The goal of this study is to elucidate the functional contribution of IP3R-Ca2+ signaling to the pathogenesis of hypertension. Our preliminary results showed that IP3R are up regulated in small mesenteric arteries of two different forms
Oxyntic cells that retain distinct morphological polarity between apical and basolateral membranes were isolated from the gastric mucosa of the amphibian Necturus. Patch-clamp techniques were applied to these cells to identify apical membrane ion channels associated with hydrochloric acid secretion. A single class of voltage-dependent, inwardly rectifying chloride channels was observed in the apical membranes of both resting and stimulated (acid-secreting) oxyntic cells. Stimulation of the cells with dibutyryladenosine 3,5-monophosphate and isobutylmethylxanthine increased channel open probability and simultaneously increased apical membrane surface area. This chloride channel is probably responsible for electrogenic chloride secretion by the gastric mucosa and may also participate in the fluid- and enzyme-secretory functions of the oxyntic cell, analogous to the chloride channels found in the apical membranes of other exocrine cells. ...
Imbalance of signals that control cell survival and death results in pathologies, including cancer and neurodegeneration. Two pathways that are integral to setting the balance between cell survival and cell death are controlled by lipid-activated protein kinase B (PKB)/Akt and Ca2+. PKB elicits its effects through the phosphorylation and inactivation of proapoptotic factors. Ca2+ stimulates many prodeath pathways, among which is mitochondrial permeability transition. We identified Ca2+ release through inositol 1,4,5-trisphosphate receptor (InsP3R) intracellular channels as a prosurvival target of PKB. We demonstrated that in response to survival signals, PKB interacts with and phosphorylates InsP3Rs, significantly reducing their Ca2+ release activity. Moreover, phosphorylation of InsP3Rs by PKB reduced cellular sensitivity to apoptotic stimuli through a mechanism that involved diminished Ca2+ flux from the endoplasmic reticulum to the mitochondria. In glioblastoma cells that exhibit hyperactive ...
In mature mammalian muscle, the chloride conductance of the membrane is an important factor in the regulation of excitability. Up to now, no ligand was available for the biochemical characterization of muscle chloride channels. In order to localize and characterize these channels, we have used indanyloxyacetic acid (IAA)-94, a ligand previously used for epithelial Cl- channels (Landry, D. W., Reitman, M., Cragoe, E. J., Jr., and Al-Awqati, Q. (1987) J. Gen. Physiol. 90, 779-798; Landry, D. W., Akabas, M. H., Redhead, C., Edelman, A., Cragoe, E. J., Jr., and Al-Awqati, Q. (1989) Science 244, 1469-1472). IAA induced myotonic responses when microinjected into mature mouse muscle fibers, indicating a blockade of Cl- channels from the cytoplasmic side. Membrane vesicles were prepared from rabbit skeletal muscle and separated by sucrose gradient centrifugation. Fractions obtained (in the order of increasing density) were sarcolemma (SL), T-tubules (TT), sarcoplasmatic reticulum (SR), and triads and ...
Shikonin is a major component of a Chinese herbal medicine named zicao. Shikonin is a potent TMEM16A chloride channel inhibitor with an IC50 of 6.5 μM. Shikonin is a specific pyruvate kinase M2 (PKM2) inhibitor and can also inhibit TNF-α and NF-κB pathway. - Mechanism of Action & Protocol.
This material is based upon work supported by the National Science Foundation under STROBE Grant No. DMR 1548924. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation ...
The recently identified TMEM16/anoctamin protein family includes Ca(2+)-activated anion channels (TMEM16A, TMEM16B), a cation channel (TMEM16F) and proteins with unclear function. TMEM16 channels consist of eight putative transmembrane domains (TMs) with TM5-TM6 flanking a re-entrant loop thought to form the pore. In TMEM16A this region has also been suggested to contain residues involved in Ca(2+) binding. The role of the putative pore-loop of TMEM16 channels was investigated using a chimeric approach. Heterologous expression of either TMEM16A or TMEM16B resulted in whole-cell anion currents with very similar conduction properties but distinct kinetics and degrees of sensitivity to Ca(2+). Furthermore, whole-cell currents mediated by TMEM16A channels were ∼six times larger than TMEM16B-mediated currents. Replacement of the putative pore-loop of TMEM16A with that of TMEM16B (TMEM16A-B channels) reduced the currents by ∼six-fold, while the opposite modification (TMEM16B-A channels) produced a ∼six
Dr. Lily Jan defines the physiological role of ion channels, like potassium channels and Calcium-Activated Chloride Channels, in the regulation of excitability in neurons.
Fusion protein amino acids 568-746 (C-terminus) of rat Clcn5 (also known as H(+)/Cl(-) exchange transporter 5, Chloride channel protein 5, Chloride transporter ClC-5, Clc5 and CLCK2, accession number P51796)Mouse: 99% identity (178/179 amino acids identical)Human: 98% identity (177/179 amino acids identical)70% identit
Catalysis of facilitated diffusion of a chloride (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism.
The CLC protein family comprises both Cl(-) channels and H(+) -coupled anion transporters. The understanding of the critical role of CLC proteins in a number of physiological functions has greatly contributed to a revision of the classical paradigm that attributed to Cl(-) ions only a marginal role in human physiology. The endosomal ClC-5 and the lysosomal ClC-7 are the best characterized human CLC transporters. Their dysfunction causes Dents disease and osteopetrosis, respectively. It had been originally proposed that they would provide a Cl(-) shunt conductance allowing efficient acidification of intracellular compartments. However, this model seems to conflict with the transport properties of these proteins and with recent physiological evidence. Currently, there is no consensus on their specific physiological role. CLC proteins present also a number of peculiar biophysical properties, such as the dimeric architecture, the co-existence of intrinsically different thermodynamic modes of transport
Myotonia is a state of hyperexcitability of skeletal-muscle fibres. Mutations in the ClC-1 Cl− channel cause recessive and dominant forms of this disease. Mutations have been described throughout the protein-coding region, including three sequence variations (A885P, R894X and P932L) in a distal C-terminal stretch of residues [CTD (C-terminal domain) region] that are not conserved between CLC proteins. We show that surface expression of these mutants is reduced in Xenopus oocytes compared with wild-type ClC-1. Functional, biochemical and NMR spectroscopy studies revealed that the CTD region encompasses a segment conserved in most voltage-dependent CLC channels that folds with a secondary structure containing a short type II poly-proline helix. We found that the myotonia-causing mutation A885P disturbs this structure by extending the poly-proline helix. We hypothesize that this structural modification results in the observed alteration of the common gate that acts on both pores of the channel. ...
Cystic fibrosis occurs due to mutation of the chromosome 7 which lead to defect in the chloride ion channel membrane ( CFTR). The common form of mutation is the ΔF508. The defect in the chloride ion channel membrane may lead to the defect in the trans
Although these experiments use cells that heterologously express CaV1.3 and hBest1, it is very likely that our results are physiologically relevant to RPE cell function. Human RPE cells and the RPE cell line ARPE-19 express CaV α1.3 and β2 subunits (Wimmers et al., 2008). Furthermore, it has been shown recently that hBest1 coimmunoprecipitates with CaVβ subunits from freshly isolated human RPE cells (Strauss et al., 2008). These results suggest that it is likely that the interaction between hBest1 and CaV subunits has an important physiological function and may help resolve the present controversy of whether Best1 is a Cl− channel (Hartzell et al., 2008).. As reviewed in the Introduction, there is strong evidence that bestrophins are Cl− channels (Hartzell et al., 2008), but this idea has been questioned (Marmorstein et al., 2004a,b, 2006; Rosenthal et al., 2005; Marmorstein and Kinnick, 2007). These authors have proposed that hBest1 is not a Cl− channel but rather is a regulator of ...
TY - JOUR. T1 - Phylogenetic shadowing of a histamine-gated chloride channel involved in insect vision. AU - Iovchev, M. AU - Boutanaev, A. AU - Ivanov, I. AU - Wolstenholme, A. AU - Nurminsky, D. AU - Semenov, E. N1 - ID number: ISI:000234767300002. PY - 2006. Y1 - 2006. N2 - A recently identified gene, hlcA (synonym: ort), codes for an ionotrophic histamine receptor Subunit in Drosophila melanogaster, and known hclA mutations lead to defects in the Visual system, neurologic disorders and changed responsiveness to neurotoxins. To investigate whether this novel class of receptors is common across the Insecta, we analysed the genomes of 15 other insect species (Diptera, Hymenoptera, Coleoptera, Lepidoptera) and revealed orthologs of hclA in all of them. The predicted receptor domain of HCLA is extensively conserved (86-100% of identity) among the 16 proteins. Minor changes in the amino acid sequence that includes the putative transmembrane domains (TMs) 1-3 were found in non-drosophilid species ...
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Looking for online definition of Chloride channel protein 5 in the Medical Dictionary? Chloride channel protein 5 explanation free. What is Chloride channel protein 5? Meaning of Chloride channel protein 5 medical term. What does Chloride channel protein 5 mean?
BACKGROUND: Dents disease, an X-linked renal tubular disorder, is characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and progressive renal failure. Dents disease results from mutations of the voltage-gated chloride channel CLC-5. METHODS: We studied the effect of zero and high citrate diet on renal function of ClC-5 knockout mice and wild-type mice. The mice were placed in metabolic cages from which the urine was collected. Mice were sacrificed to obtain serum and tissues for analysis. RESULTS: ClC-5 knockout mice fed zero or high citrate diet had significantly increased urinary calcium excretion compared with wild-type mice fed the same diets. Nine-month-old ClC-5 knockout mice on a zero citrate diet had significantly decreased glomerular filtration rate (GFR), whereas 9-month-old ClC-5 knockout mice on a high citrate diet had normal renal function. ClC-5 knockout mice fed a zero citrate diet had significantly increased tubular atrophy, ...
TY - JOUR. T1 - Role of calcium in volume-activated chloride currents in a mouse cholangiocyte cell line. AU - Chen, Biyi. AU - Nicol, Grant. AU - Cho, Won Kyoo. PY - 2007/1/1. Y1 - 2007/1/1. N2 - Volume-activated Cl- channels (VACCs) play vital roles in many cells including cholangiocytes. Previously, we characterized the VACCs in mouse cholangiocytes. Since calcium plays an important role in VACC regulation in many cells, we have studied the effect of calcium modulation on the regulatory volume decrease (RVD) and VACC currents in mouse bile duct cells (MBDCs). Cell volume measurements were assessed by a Coulter counter with cell sizer, and conventional whole-cell patch-clamp techniques were used to study the role of calcium on RVD and VACC currents. Cell volume study indicated that MBDCs exhibited RVD, which was inhibited by 5-nitro-2′-(3-phenylpropylamino)- benzoate (NPPB), 4,4′-diisothiocyanostilbene-2,2′-disulfonate (DIDS) and 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic ...
Regulation of Epithelial Chloride Channels: Implications for Cell Volume Regulation and Cystic Fibrosis A Thesis Submitted to the Faculty of the Department of Physiology In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy by Erik M. Schwiebert DARTMOUTH COLLEGE Hanover, New Hampshire January, 1993 ...
X-linked recessive NEPHROLITHIASIS characterized by HYPERCALCIURIA; HYPOPHOSPHATEMIA; NEPHROCALCINOSIS; and PROTEINURIA. It is associated with mutations in the voltage-gated chloride channel, CLC-5 (Dent Disease I). Another group of mutations associated with this disease is in phosphatidylinositol 4,5-bisphosphate-5-phosphatase gene ...
Abstract: : Purpose: In corneal endothelial cells, apical HCO3- permeability can be enhanced by increasing [Ca2+]i via either activation of purinergic receptor or inhibition of the sarcoendoplasmic reticulum calcium-ATPase ( SERCA ). Our goal is to identify the molecular candidate of the calcium-activated anion channel. Methods: Fresh and cultured bovine corneal endothelial cells ( FBCEC, CBCEC) were used in the study. A probe containing the first 457bp of the bCLCA1 open reading frame was used for in situ hybridization analysis. A 15 aa polypeptide (417-431) conjugate was used to generate polyclonal antibodies in rabbit. The immunoblot and immunofluoresence assay were performed to detect the protein expression of bCLCA1. Results: In situ hybridization with the bCLCA1-specific probe confirmed prominent mRNA expression in CBCEC. In immunoblot assay, the antiserum detects the heterologously expressed bCLCA1in HEK293 cell line, which was transfected with pcDNA3.1-bCLCA1 (a gift from Dr. Fuller in ...
Apical membrane chloride channels control chloride secretion by airway epithelial cells. Defective regulation of these channels is a prominent characteristic of cystic fibrosis. In normal intact cells, activation of protein kinase C (PKC) by phorbol ester either stimulated or inhibited chloride secretion, depending on the physiological status of the cell. In cell-free membrane patches, PKC also had a dual effect: at a high calcium concentration, PKC inactivated chloride channels; at a low calcium concentration, PKC activated chloride channels. In cystic fibrosis cells, PKC-dependent channel inactivation was normal, but activation was defective. Thus it appears that PKC phosphorylates and regulates two different sites on the channel or on an associated membrane protein, one of which is defective in cystic fibrosis. ...
TY - JOUR. T1 - Chloride equilibrium potential in salamander cones. AU - Thoreson, Wallace B. AU - Bryson, Eric J.. PY - 2004/12/5. Y1 - 2004/12/5. N2 - Background: GABAergic inhibition and effects of intracellular chloride ions on calcium channel activity have been proposed to regulate neurotransmission from photoreceptors. To assess the impact of these and other chloride-dependent mechanisms on release from cones, the chloride equilibrium potential (ECl) was determined in red-sensitive, large single cones from the tiger salamander retinal slice. Results: Whole cell recordings were done using gramicidin perforated patch techniques to maintain endogenous Cl- levels. Membrane potentials were corrected for liquid junction potentials. Cone resting potentials were found to average -46 mV. To measure ECl, we applied long depolarizing steps to activate the calcium-activated chloride current (ICl(Ca)) and then determined the reversal potential for the current component that was inhibited by the Cl- ...
Mammary gland regression at the cessation of lactation (involution) is an exquisitely orchestrated process of cell death and tissue remodelling in which Stat3 signalling has an essential role. The involution microenvironment of the mammary gland is considered to be pro-tumourigenic and a proportion of cases of pregnancy-associated breast cancer are suggested to originate in tandem with involution. However, the apparent paradox that STAT3 is required for cell death in normal mammary gland, but is associated with breast cancer cell survival, has not been resolved. Herein, we investigate Stat3-mediated regulation of expression of members of the calcium-activated chloride channel regulator (CLCA) family of proteins during involution and mammary carcinogenesis. Using the conditionally immortal mammary epithelial cell line KIM-2, together with mice exhibiting mammary epithelial cell-specific deletion of Stat3 during lactation, we demonstrate that expression of mCLCA1 and mCLCA2 is elevated in concert ...
This gene encodes a member of the bestrophin gene family. This small gene family is characterized by proteins with a highly conserved N-terminus with four to six transmembrane domains. Bestrophins may form chloride ion channels or may regulate voltage-gated L-type calcium-ion channels. Bestrophins are generally believed to form calcium-activated chloride-ion channels in epithelial cells but they have also been shown to be highly permeable to bicarbonate ion transport in retinal tissue. Mutations in this gene are responsible for juvenile-onset vitelliform macular dystrophy (VMD2), also known as Best macular dystrophy, in addition to adult-onset vitelliform macular dystrophy (AVMD) and other retinopathies. Alternative splicing results in multiple variants encoding distinct isoforms ...
Niflumic acid inhibits Ca2+-activated Cl- channels with inhibition constant of 17 mM. Niflumic acid also inhibits ICl(Ca) elicited by bath application of Ca2+ to oocytes permeabilized using the Ca2+ ionophore A23187, demonstrating that the inhibition of ICl(Ca) is due to a direct interaction with the Cl- channel, rather than by interference with Ca2+ entry through voltage-dependent Ca2+ channels. [1] Niflumic acid blocks Ca2+-activated non-selective cation channels in inside-out patches from the basolateral membrane of rat exocrine pancreatic cells with IC50 of 50 μM. [2] Niflumic acid dose-dependently and reversibly activates large conductance calcium-activated K+ (KCa) channels. [3] Niflumic acid produces a concentration-dependent inhibition of spontaneous transient inward current (STIC, calcium-activated chloride current) amplitude. Niflumic acid inhibits noradrenaline- and caffeine-evoked IO(Ca) with an ICM50 of 6.6 μM, i.e.is less potent against evoked currents compared to spontaneous ...
TY - JOUR. T1 - Apical membrane chloride channels in a colonic cell line activated by secretory agonists. AU - Halm, D. R.. AU - Rechkemmer, G. R.. AU - Schoumacher, Robert. AU - Frizzell, R. A.. PY - 1988/1/1. Y1 - 1988/1/1. N2 - We characterized the anion channel responsible for the increase in apical membrane Cl secretion using a model salt-secreting epithelium, the T84 colonic cell line. The adenosine 3,5-cyclic monophosphate (cAMP)-mediated secretagogues, prostaglandin E2, forskolin, and 8-bromo-cAMP, evoked activity of an outwardly rectifying Cl channel in previously quiet cell-attached membrane patches. The channel remained active in excised, inside-out membranes, where its single-channel conductance was 40-45 pS at 0 mV with 160 mM NaCl in pipette and bath. Selectivities were P(Cl)/P(Na) = 50 and for halides I(1.8)/Br(1.4)/Cl(1.0)/F(0.4). This halide sequence illustrates that the ability of various anions to undergo transepithelial secretion is determined by the selectivity of the ...
SGLT1-based oral rehydration solution (ORS) used in the management of acute diarrhoea does not substantially reduce stool output, despite the fact that glucose stimulates the absorption of sodium and water. To explain this phenomenon, we investigated the possibility that glucose might also stimulate anion secretion. Transepithelial electrical measurements, isotope flux measurements in Ussing chambers, fluid movement in isolated ileal sacs and electrical measurements in patch clamp studies were used to study the effect of glucose on active chloride and fluid secretion in mouse small intestinal cells and human Caco-2 cells. Confocal fluorescence laser microscopy and immunohistochemistry measured intracellular changes in calcium, SGLT1 and calcium-activated chloride channel (anoctamin 1) expression. In addition to enhancing active sodium absorption, glucose increased intracellular calcium and stimulated electrogenic chloride secretion. Calcium imaging studies showed increased intracellular calcium ...
The data presented above indicate that Ano6, 8 and 9, when overexpressed in HEK293 cells, produce Cl− currents upon increase in intracellular Ca2+ by ionomycin. However, although all three paralogs are expressed endogenously in HEK293 cells, no currents are activated in mock-transfected cells (Fig. 3A) (Almaça et al., 2009). However, when increasing [Ca2+]i to very high levels (≥10 µM), endogenous anoctamins were activated (Fig. 3B,E). This may be due to a lack of sufficient membrane expression of endogenous anoctamins. Endogenous anoctamins are expressed at much lower levels than overexpressed proteins and may be inhibited by endogenous accessory proteins, such as CAMKII. Alternatively, specific Ca2+ release and/or influx pathways need to be triggered to activate these endogenous anoctamins. The overall linear structures appear similar in all anoctamins (supplementary material Fig. S1) and an analysis of putative functional domains revealed a number of similar motifs and putative ...
Tumor necrosis factor alpha inhibits signaling from the insulin receptor.. The medical assessment for police officer special constable police community support Diabetes. The Australasian Diabetes in Pregnancy Society consensus guidelines for the management of diabetes information websites breakfast meals type 1 and type 2 diabetes in relation to pregnancy Potassium Channels and Calcium-Activated Chloride Channels: and control of hormone release from endocrine tissues. Healthy diet and lifestyle choices form the basis of managing diabetes.. Q: Do mosquitoes prefer certain people over others? I could swear I always get bitten up more than my friends do when were together! Yes they do! canadian pharmacy insulin. If the blood sugar level Diabetes Journal Letter Tracker Test falls too low energy supply to all tissues particularly the ain is impaired. Wartenberg responded: Yes sometimes. What is insulin pump therapy? Insulin pumps use only et al. NICE - Endorsed Clinical Guidelines ...
Chloride channels (ClCs) have gained worldwide interest because of their molecular diversity, widespread distribution in mammalian tissues and organs, and their link to various human diseases. Nine different ClCs have been molecularly identified and functionally characterized in mammals. ClC-2 is one of nine mammalian members of the ClC family. It possesses unique biophysical characteristics, pharmacological properties, and molecular features that distinguish it from other ClC family members. ClC-2 has wide organ/tissue distribution and is ubiquitously expressed. Published studies consistently point to a high degree of conservation of ClC-2 function and regulation across various species from nematodes to humans over vast evolutionary time spans. ClC-2 has been intensively and extensively studied over the past two decades, leading to the accumulation of a plethora of information to advance our understanding of its pathophysiological functions; however, many controversies still exist. It is necessary to
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Introduction: Adult hearts contain c-Kit+ endogenous cardiac stem cells (eCSCs) that are being studied for regenerative therapy. eCSCs express volume-dependent Cl- channels (ICl,vol) activated under hemodynamic stress. Here, we examined the changes in eCSC Cl- channels caused by experimental congestive heart failure (CHF).. Methods: c-Kit+ eCSCs isolated from healthy (CTL) and CHF (tachypaced) dog hearts were magnetically purified with c-Kit antibodies. Cl- channel expression in freshly isolated cells was studied with patch clamp and qPCR.. Results: Under isotonic conditions, ionic currents were barely detectable in CTL eCSCs (Fig. A). The current observed was time-independent and reversed at values close to the calculated Cl- equilibrium potential (ECl-≈ -40 mV). This current was insensitive to TEA-Cl but inhibited by the Cl- channel blocker DIDS. When cells were superfused with hypo-osmotic solution (0.7T), an outward current with unchanged reversal potential was activated, and completely ...
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This chapter reviews the well-characterized genetic syndromes of bacterial susceptibility with an eye toward specificity of the susceptibility, applicability of the defect to infections in the general population, and, where applicable, treatment. Defects in barriers involving the skin and lung and defects of leukocyte number, trafficking, and function are also considered in this chapter. The major protection afforded by the skin is due to the stratum corneum, which provides a multifunctional barrier retarding water loss and providing an antimicrobial barrier. Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), the gene that encodes the major epithelial chloride channel. This chapter focuses on examples of innate immune defects, especially those involving phagocytic cells as mutations in the genes regulating the innate immune system have been very informative regarding the specific associations of genes and
Chloride channel accessory 1 is a protein that in humans is encoded by the CLCA1 gene. This gene encodes a member of the calcium sensitive chloride conductance protein family. To date, all members of this gene family map to the same region on chromosome 1p31-p22 and share a high degree of homology in size, sequence, and predicted structure, but differ significantly in their tissue distributions. The encoded protein is expressed as a precursor protein that is processed into two cell-surface-associated subunits, although the site at which the precursor is cleaved has not been precisely determined. The encoded protein may be involved in mediating calcium-activated chloride conductance in the intestine. Protein structure prediction methods suggest the N-terminal region of CLCA1 protein is a zinc metalloprotease. Chloride channel GRCh38: Ensembl release 89: ENSG00000016490 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000028255 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed ...
A bicyclic fatty acid derived from prostaglandin E1 and a chloride channel activator with laxative activity. Upon intake, lubiprostone specifically binds to and activates the type 2 chloride channel (ClC-2) in the apical membrane of the gastrointestinal epithelium. This produces an efflux of chloride ions, thereby drawing water into the gastrointestinal lumen. The resulting increased amounts of intestinal fluid soften the stool, increase motility, and improve bowel movements.
Ivermectin is a large lipophilic molecule that acts as a positive allosteric regulator of several ligand-gated channels including the glutamate-gated chloride channel, gamma aminobutyric acid type-A receptor, glycine receptor, neuronal alpha7-nicotinic receptor and purinergic P2X4 receptor. This review summarizes what is currently known about ivermectin binding and modulation of Cys-loop receptor family of ligand-gated ion channels and what are the critical structural determinants underlying potentiation of the P2X4 receptor channel. Více ...
We have shown that XE991 can reduce electrogenic chloride secretion in the murine colon when it is added basolaterally. This result supports the general thesis that hyperpolarization increases chloride efflux through the apical membrane by increasing the electrical gradient. Conversely, blockade of basolateral K+-channels, by causing depolarization, will reduce chloride secretion. Because XE991 reduces the basal SCC without prior stimulation of SCC, this suggests that some K+ channels are constitutively open, as has been argued by others (Schroeder et al., 2000).. Both forskolin and EBIO have multiple actions on chloride secretory epithelia. Both activate apically located CFTR chloride channels, either by increasing cAMP (Cuthbert et al., 1999b) or by direct action (Devor et al.,1996a,b), and both activate basolateral K+ channels, again either via cAMP or by a mixture of direct and indirect actions (Devor et al.,1996a,b; Cuthbert et al., 1999b; Syme et al., 2000). However, as shown here for the ...
CLC-5, the chloride channel mutated in Dents disease, colocalizes with the proton pump in endocytotically active kidney cells ...
This study reports the formation of self-assembled transmembrane anion channels by small-molecule fumaramides. Such artificial ion channel formation was confirmed by ion transport across liposomes and by planar bilayer conductance measurements. The geometry-optimized model of the channel and Cl− ion selectivity wit
Membrane Protein Disease, Innate Immunity. Plasma membrane (PM) proteins including signaling receptors, ion channels and transporters play crucial roles in physiological functions of cells and organisms. Genetic and environmental stresses cause the defective expression of PM proteins that is associated with several human diseases such as cystic fibrosis (CF). The ultimate goal in our research is to elucidate the molecular and cellular mechanisms underlying the defective expression of PM proteins and to help develop novel therapeutic approaches for human diseases.. Right now, we focus on the CFTR chloride channel associated with CF, one of the most common genetic diseases in Caucasians. While the most common CFTR mutant in CF patients has the ability to function as a chloride channel, it is rapidly eliminated by proteolysis through cellular quality control systems including the PM quality control mechanism that we originally identified. We are interested in understanding the molecular and ...
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A high-affinity specific binding site is reported for [3H]AVM B1a with K Dvalues of 1.4 nM as a rough estimate for dog brain (Pong and Wang, 1980) and 2.5 nM for rat cerebellar cortex (Drexler and Sieghart, 1984a) and for its dihydro analog [3H]ivermectin with aK D value of 22 nM for rat cerebral cortex (Schaeffer and Haines, 1989). In our preliminary study, we found that the specific binding sites for AVM B1a are widely distributed in rat whole brain but particularly enriched in the cerebellum, which is consistent with the findings of Pong and Wang (1980). We then evaluated the binding properties of [3H]AVM B1a in primary cultures of cerebellar neurons and directly investigated the effects of AVM B1a on the GABA-gated chloride channel with [3H]EBOB binding and36Cl− influx as indicators. The use of intact neuron cultures made it possible to perform radioligand binding and functional assays of 36Cl−influx in comparable and physiological conditions.. Specific binding of [3H]AVM B1a in intact ...
Benzodiazepines act at omega modulatory sites, which are part of the GABAA-omega modulatory site- chloride ions channel receptor complex. It is a multimeric membrane protein constitued by the assembly of a, b, g, d and r subunits, the a subunit carrying ...
Furthermore to these suggestions, diagnostic requirements including history of hepatitis; imaging features as given by the Liver organ Imaging Confirming and Data Program (LI-RADS) that are of help in evaluation of RHCC; previous RHCC recognition using BALAD and GALAD ratings; risk elements predicting RHCC after major resection; hepatectomy methods that lessen recurrence; and adjuvant treatments including antiviral real estate agents, molecular targeted therapy, systemic chemotherapy, and immunotherapy are referred to. Until now, proof supporting most therapeutic options for RHCC has been limited to cohort investigations. Randomized controlled studies have been few. Treatments have not been compared in terms of use at specific tumor stages. As a result, treatments useful for major tumors including medical resection frequently, liver organ transplantation, TACE, regional ablative therapy, and radiotherapy have already been put on recurrences empirically. As opposed to RHCC, many treatment ...
Background In certain parts of Africa, type-specific HSV type-2 ELISAs may have limited specificity. check had been 92% and 79%, respectively, versus the WB; and 80% and 82% versus the Apremilast inhibition check. Rabbit polyclonal to APBA1. Using the inhibition check as the guide standard, the awareness from the WB made an appearance low (49%). Conclusions In HIV-seronegative guys in american Kenya, the Kalon and HerpeSelect type-specific ELISAs got high sensitivities however small specificities using the WB as reference standard. General, the Kalon ELISA performed much better than the HerpeSelect ELISA in these teenagers from Kisumu. Additional understanding Apremilast is Apremilast necessary for the interpretation of HSV-2 ELISA or inhibition test positive/WB seronegative outcomes. Before HSV-2 seropositivity could be reported in chosen regions of Africa reliably, performance research of HSV-2 serological assays in person physical areas are suggested. Summary Using Western-blot as the ...
Moral-Sanz, J., Mahmoud, A. D., Ross, F. A., Eldstrom, J., Fedida, D., Hardie, D. G. & Evans, A. M. 1 Sep 2016 In : Journal of Physiology. 594, 17, p. 4901-4915 15 p.. Research output: Contribution to journal › Article ...
Zhang CH, Wang P, Liu DH, Chen CP, Zhao W, Chen X, Chen C, He WQ, Qiao YN, Tao T, Sun J, Peng YJ, Lu P, Zheng K, Craige SM, Lifshitz LM, Keaney JF, Fogarty KE, ZhuGe R, Zhu MS. The molecular basis of the genesis of basal tone in internal anal sphincter. Nat Commun. 2016 Apr 22; 7:11358 ...
Order Bestrophin 4 ELISA Kits for many Reactivities. and more. Compare Bestrophin 4 ELISA Kits and find the right product on antibodies-online.com.
Recent studies of the mechanisms underlying the bestrophinopathies indicate that four degenerative retinal diseases are associated with disparate effects on bestrophin-1 localization, but not oligomerization. Stem cell donors are needed for further research into a cure for Best disease.
The CLCN1 gene provides instructions for making a type of protein called a chloride channel. Learn about this gene and related health conditions.
Synonyms for acetyl chloride in Free Thesaurus. Antonyms for acetyl chloride. 1 synonym for acetyl chloride: ethanoyl chloride. What are synonyms for acetyl chloride?
This gene encodes a serine/threonine protein kinase that plays an important role in cellular stress response. This kinase activates certain potassium, sodium, and chloride channels, suggesting an involvement in the regulation of processes such as cell survival, neuronal excitability, and renal sodium excretion. High levels of expression of this gene may contribute to conditions such as hypertension and diabetic nephropathy. Several alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2009 ...
Complete information for CLCN6 gene (Protein Coding), Chloride Voltage-Gated Channel 6, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for CLCN2 gene (Protein Coding), Chloride Voltage-Gated Channel 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
eBiochemicals provides information on the 3-Methylbenzoyl chloride(m-Toluoyl chloride; m-Methylbenzoyl chloride; 3-methylbenzoyl chloride): structure, NMR,MS,IR,spectral data, msds, molecular formula, cas, physical and chemical properties, and suppliers.
N,N-Diethylcarbamothioic chloride; Diethylcarbamothioyl chloride; Diethylthiocarbamoyl chloride; Diethylthiocarbamyl chloride; N,N-Diethylthiocarbamoyl ...
There are no specific protocols for QX-314 chloride (|em|N|/em|-Ethyllidocaine chloride) (ab120118). Please download our general protocols booklet
Alfa Aesar™ 4-Chloro-2-fluoro-3-methoxybenzoyl chloride, 97% 1g Alfa Aesar™ 4-Chloro-2-fluoro-3-methoxybenzoyl chloride, 97% Chlorofluorobenzi to...
Alfa Aesar™ 4-Chlorobutyryl chloride, 98% 1000g Alfa Aesar™ 4-Chlorobutyryl chloride, 98% Chlorot to Chola -Organics
First, m-cresol, chlorobenzene, sodium hydroxide, potassium hydroxide, and copper chloride react to yield m-phenoxytoluene. ...
Cl−: Chloride channel. *Calcium-activated chloride channels *Anoctamin *ANO1. *Bestrophin *1. *2 ... calcium channel activity. • metal ion binding. • voltage-gated ion channel activity. • ion channel activity. • protein binding ... voltage-gated calcium channel activity involved in cardiac muscle cell action potential. • high voltage-gated calcium channel ... When calcium ions bind to calmodulin, which in turn binds to a Cav1.2 channel, it allows the Cav1.2 channels within a cluster ...
Cl−: Chloride channel. *Calcium-activated chloride channels *Anoctamin *ANO1. *Bestrophin *1. *2 ... ion channel activity. • protein binding. • actin binding. • calcium channel activity. • cation channel activity. • protein ... Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene encoding a protein of ... cation channel complex. Biological process. • regulation of cytosolic calcium ion concentration. • positive regulation of ...
Cl−: Chloride channel. *Calcium-activated chloride channels *Anoctamin *ANO1. *Bestrophin *1. *2 ... Inositol trisphosphate receptor (InsP3R) is a membrane glycoprotein complex acting as a Ca2+ channel activated by inositol ...
Cl−: Chloride channel. *Calcium-activated chloride channels *Anoctamin *ANO1. *Bestrophin *1. *2 ... gap junction channel activity. Cellular component. • cytoplasm. • integral component of membrane. • gap junction. • cell ... Connexins are membrane-spanning proteins that assemble to form gap junction channels that facilitate the transfer of ions and ... Typically the GJB1 protein forms channels through the myelin to the internal Schwann cell or oligodendrocyte, allowing ...
Cl−: Chloride channel. *Calcium-activated chloride channels *Anoctamin *ANO1. *Bestrophin *1. *2 ... Channel composition influences the function of gap junction channels. Before innexins and connexins were well characterized, ... When two identical hemichannel proteins come together to form a Gap junction channel, it is called a homotypic GJ channel. When ... One gap junction channel is composed of two protein heximers (or hemichannels) called connexons in vertebrates and innexons in ...
Cl−: Chloride channel. *Calcium-activated chloride channels *Anoctamin *ANO1. *Bestrophin *1. *2 ... voltage-gated ion channel activity. • channel regulator activity. • calcium channel activity. • voltage-gated calcium channel ... Voltage-dependent calcium channel gamma-4 subunit is a protein that in humans is encoded by the CACNG4 gene.[5][6] ... voltage-gated calcium channel complex. • integral component of membrane. • integral component of plasma membrane. • AMPA ...
Cl−: Chloride channel. *Calcium-activated chloride channels *Anoctamin *ANO1. *Bestrophin *1. *2 ... ion channel activity. • store-operated calcium channel activity. • protein binding. • calcium channel activity. • clathrin ... calcium channel complex. • membrane. • cytoplasm. • growth cone. • neuronal cell body. • dendrite. • membrane raft. • cation ... Short transient receptor potential channel 5 (TrpC5) also known as transient receptor protein 5 (TRP-5) is a protein that in ...
Cl−: Chloride channel. *Calcium-activated chloride channels *Anoctamin *ANO1. *Bestrophin *1. *2 ... channel), voltage gated potassium channel HBK1, voltage gated potassium channel subunit Kv1.1, voltage-gated K+ channel HuKI ... potassium channel activity. • delayed rectifier potassium channel activity. • voltage-gated ion channel activity. • GO:0015388 ... Potassium voltage-gated channel subfamily A member 1 also known as Kv1.1 is a shaker related voltage-gated potassium channel ...
Cl−: Chloride channel. *Calcium-activated chloride channels *Anoctamin *ANO1. *Bestrophin *1. *2 ... calcium channel activity. • metal ion binding. • voltage-gated ion channel activity. • voltage-gated calcium channel activity. ... Voltage-dependent calcium channel subunit alpha2delta-2 is a protein that in humans is encoded by the CACNA2D2 gene.[5] ... voltage-gated calcium channel complex. • integral component of membrane. • membrane. • plasma membrane. ...
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 ... GluCls are invertebrate-specific members of the Cys-loop family of ligand-gated ion channels present in neurons and myocytes. ...
Chloride channel. *Ivermectin. Sulfur-containing products. *Disulfiram. *Dixanthogen. *Mesulfen. *Thiram. Chlorine-containing ...
These chloride channels have an important role in the control of membrane excitability, transepithelial transport, and possibly ... CLCN5 belongs to the family of voltage-gated chloride channel genes (CLCN1-CLCN7, CLCKa and CLCKb) that have about 12 ... Jentsch TJ, Friedrich T, Schriever A, Yamada H (May 1999). "The CLC chloride channel family". Pflugers Arch. 437 (6): 783-95. ... August 2000). "Characterization of renal chloride channel (CLCN5) mutations in Dent's disease". J. Am. Soc. Nephrol. 11 (8): ...
Avermectins target the alpha subunit of glutamate-gated chloride channels with high affinity. These receptors have also been ... In arthropods and nematodes, glutamate stimulates glutamate-gated chloride channels. The β subunits of the receptor respond ... Wolstenholme, Adrian J. (2012-11-23). "Glutamate-gated Chloride Channels". The Journal of Biological Chemistry. 287 (48): 40232 ... and glutamate-gated chloride channel (GluCl) alpha receptor subunits in sea lice (Lepeophtheirus salmonis)". Journal of ...
Ghosh, R.; Andersen, E. C.; Shapiro, J. A.; Gerke, J. P.; Kruglyak, L. (2012-02-02). "Natural Variation in a Chloride Channel ... Wolstenholme, Adrian J. (2012-10-04). "Glutamate-gated Chloride Channels". Journal of Biological Chemistry. American Society ... Bloomquist, Jeffrey R. (2003). "Chloride channels as tools for developing selective insecticides". Archives of Insect ... L-glutamate-gated chloride channel subunit from Caenorhabditis elegans". British Journal of Pharmacology. Wiley. 132 (6): 1247- ...
... encodes one of the two major chloride channels found in the kidney, the ClC-Ka channel (the other class being the ClC-Kb ... Chloride channel BSND, barttin, accessory subunit beta for this channel GRCh38: Ensembl release 89: ENSG00000186510 - Ensembl, ... "Entrez Gene: CLCNKA chloride channel Ka". Barlassina C, Dal Fiume C, Lanzani C, Manunta P, Guffanti G, Ruello A, Bianchi G, Del ... Chloride channel protein ClC-Ka is a protein that in humans is encoded by the CLCNKA gene. Multiple transcript variants ...
Chlorotoxin from the deathstalker scorpion (Leiurus quinquestriatus); the toxin blocks small-conductance chloride channels; ... "Chloride channel inhibition by the venom of the scorpion Leiurus quinquestriatus". Toxicon. 29 (11): 1403-1408. doi:10.1016/ ... An important physiological role of the KCNA3 channel, also known as KV1.3, is to help maintain large electrical gradients for ... Short-chain scorpion toxins constitute the largest group of potassium (K+) channel-blocking peptides. ...
GABAA receptors are ligand-activated chloride channels: when activated by GABA, they allow the flow of chloride ions across the ... depends on the direction of the flow of chloride. When net chloride flows out of the cell, GABA is depolarising; when chloride ... "Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels". Nature. 341 (6239): 233-6. ... Uncompetitive antagonist (e.g. channel blocker) picrotoxin[citation needed], cicutoxin Negative allosteric modulators ...
GABAA receptors are ligand-activated chloride channels: when activated by GABA, they allow the flow of chloride ions across the ... depends on the direction of the flow of chloride. When net chloride flows out of the cell, GABA is depolarising; when chloride ... This binding causes the opening of ion channels to allow the flow of either negatively charged chloride ions into the cell or ... "Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels". Nature. 341 (6239): 233-6. ...
... channel proteins". Genomics. 54 (2): 200-14. doi:10.1006/geno.1998.5562. PMID 9828122. "Entrez Gene: CLCA1 chloride channel, ... Chloride channel accessory 1 is a protein that in humans is encoded by the CLCA1 gene. This gene encodes a member of the ... Toda M, Tulic MK, Levitt RC, Hamid Q (2002). "A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 ... Chloride channel GRCh38: Ensembl release 89: ENSG00000016490 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000028255 ...
Wu, Fiona (2014). Dent's disease and the chloride channel, CLC-5 (DPhil thesis). University of Oxford.. ...
Chloride intracellular channel protein 2 is a protein that in humans is encoded by the CLIC2 gene. Chloride channels are a ... "Entrez Gene: CLIC2 chloride intracellular channel 2". Thiemann A, Gründer S, Pusch M, Jentsch TJ (1992). "A chloride channel ... Chloride intracellular channel 2 is a member of the p64 family; the protein is detected in fetal liver and adult skeletal ... Chloride channel GRCh38: Ensembl release 89: ENSG00000155962 - Ensembl, May 2017 "Human PubMed Reference:". National Center for ...
"The swelling-activated chloride channel ClC-2, the chloride channel ClC-3, and ClC-5, a chloride channel mutated in kidney ... The CLCN5 gene encodes the chloride channel Cl-/H+ exchanger ClC-5. ClC-5 is mainly expressed in the kidney, in particular in ... Mohammad-Panah R, Harrison R, Dhani S, Ackerley C, Huan LJ, Wang Y, Bear CE (August 2003). "The chloride channel ClC-4 ... Lamb FS, Clayton GH, Liu BX, Smith RL, Barna TJ, Schutte BC (March 1999). "Expression of CLCN voltage-gated chloride channel ...
Chloride intracellular channel protein 6 is a protein that in humans is encoded by the CLIC6 gene. The CLIC6 gene encodes a ... "Entrez Gene: CLIC6 chloride intracellular channel 6". Griffon, Nathalie; Jeanneteau Freddy; Prieur Fanny; Diaz Jorge; Sokoloff ... Chloride channel GRCh38: Ensembl release 89: ENSG00000159212 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000022949 ... 2003). "CLIC6, a member of the intracellular chloride channel family, interacts with dopamine D(2)-like receptors". Brain Res. ...
The encoded protein functions as a calcium(2+)-activated large conductance chloride(-) channel, and may play a role in kidney ... Members of this family function as chloride channels. ... of the human Tweety family of putative chloride ion channels ... ligase Nedd4-2 differentially interacts with and regulates members of the Tweety family of chloride ion channels". The Journal ... Suzuki M, Mizuno A (May 2004). "A novel human Cl(-) channel family related to Drosophila flightless locus". The Journal of ...
This protein is a chloride channel. Chloride channel GRCh38: Ensembl release 89: ENSG00000169583 - Ensembl, May 2017 GRCm38: ... Chloride intracellular channel protein 3 is a protein that in humans is encoded by the CLIC3 gene. ... 1997). "Molecular cloning and expression of a chloride ion channel of cell nuclei". J. Biol. Chem. 272 (19): 12575-82. doi: ... Suginta W, Karoulias N, Aitken A, Ashley RH (2001). "Chloride intracellular channel protein CLIC4 (p64H1) binds directly to ...
Chloride intracellular channel protein 1 is a protein that in humans is encoded by the CLIC1 gene. Chloride channels are a ... CLIC1 chloride intracellular channel 1". Fan, Libin; Yu Wei; Zhu Xueliang (Apr 2003). "Interaction of Sedlin with chloride ... Chloride intracellular channel 1 is a member of the p64 family; the protein localizes principally to the cell nucleus and ... 2001). "The nuclear chloride ion channel NCC27 is involved in regulation of the cell cycle". J. Physiol. 529 (3): 541-52. doi: ...
... A can form ion channels in vitro and its channel activity is regulated by actin, though measurement of its chloride ... Chloride intracellular channel protein 5 is a protein that in humans is encoded by the CLIC5 gene. CLIC5 exists in two ... "Entrez Gene: CLIC5 chloride intracellular channel 5". Al-Momany A, Li L, Alexander RT, Ballermann BJ (December 2014). " ... Tavasoli M, Li L, Al-Momany A, Zhu LF, Adam BA, Wang Z, Ballermann BJ (April 2016). "The chloride intracellular channel 5A ...
Chloride intracellular channel 4, also known as CLIC4, is a eukaryotic gene. Chloride channels are a diverse group of proteins ... "Entrez Gene: CLIC4 chloride intracellular channel 4". Suginta W, Karoulias N, Aitken A, Ashley RH (October 2001). "Chloride ... Chloride intracellular channel 4 (CLIC4) protein, encoded by the CLIC4 gene, is a member of the p64 family; the gene is ... Duncan RR, Westwood PK, Boyd A, Ashley RH (1997). "Rat brain p64H1, expression of a new member of the p64 chloride channel ...
Anoctamin-1 is a voltage-gated calcium-activated anion channel, which acts as a chloride channel and a bicarbonate channel. ... ANO1 is a transmembrane protein that functions as a calcium-activated chloride channel. Ca2+, Sr2+, and Ba2+ activate the ... Ni YL, Kuan AS, Chen TY (2014). "Activation and inhibition of TMEM16A calcium-activated chloride channels". PLOS ONE. 9 (1): ... "Entrez Gene: anoctamin 1, calcium activated chloride channel". Katoh M, Katoh M (June 2003). "FLJ10261 gene, located within the ...
Other potassium channels like large conductance calcium-dependent potassium channels and sodium chloride dependent potassium ... The channels are regulated by G protein-coupled receptors that can activate or inhibit the NALCN channels depending on the ... NALCN sodium leak channels appear to give rise to an inward current that may play an important role in the modulation of ... L-type calcium channels are known to increase the frequency of action potentials in some neurons, which might be the reason ...
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 ... GABA-gated chloride ion channel activity. • transmitter-gated ion channel activity involved in regulation of postsynaptic ... chloride channel complex. • cell junction. • plasma membrane. • GABA-ergic synapse. • integral component of postsynaptic ...
See also: Receptor/signaling modulators • Ion channel modulators. Taxon identifiers. *Wikidata: Q146217 ... Phenacyl chloride. *Polygodial (Dorrigo pepper). *Shogaols (ginger, Sichuan and melegueta peppers). *Tear gases ...
... which is comparable to the LD50 values of potassium chloride and sodium chloride.[244] Caesium chloride has been promoted as an ... Hellgren, Mikko; Sandberg, Lars; Edholm, Olle (2006). "A comparison between two prokaryotic potassium channels (KirBac1.1 and ... The metal is produced electrolytically from a mixture of fused lithium chloride and potassium chloride.[183] ... potassium chloride).[30] Previously, potassium was generally made from the electrolysis of potassium chloride or potassium ...
Upon binding, it triggers the GABAA receptor to open its chloride channel to allow chloride ions into the neuron, making the ... Additionally, in the absence of GABA the presence of benzodiazepines alone does not open the chloride channel.[2] ... the chloride (Cl-) ion channel pore, the two GABA active binding sites at the α1 and β2 interfaces, and the benzodiazepine (BZD ... But if the γ2 is expressed with α1 and β2 the sensitivity is low and channel conductance is high.[7] γ2 subunit has to be ...
Gold(I) chloride has been used as co-catalyst combined with palladium(II) chloride in the coupling of arenediazonium salts with ... "A Practical and Efficient Synthesis of the Selective Neuronal Acetylcholine-Gated Ion Channel Agonist (S)-(−)-5-Ethynyl-3-(1- ... chloride are used. Copper(I) salts, such as copper iodide, react with the terminal alkyne and produce a copper(I) acetylide, ... and of aryl chlorides, but in very low yields. The dendrimeric catalysts could usually be recovered by simple precipitation and ...
States in which ginger is exported follow the marketing channels of vegetable marketing in India, and the steps are similar to ... Phenacyl chloride. *Polygodial (Dorrigo pepper). *Shogaols (ginger, Sichuan and melegueta peppers). *Tear gases ... water channels are made 60-80 ft apart to irrigate the crop.[29] ... See also: Receptor/signaling modulators • Ion channel ...
Calcium Channel Blockers. CCB. 降血壓. 鈣質. Calcium. -. 骨骼細胞營養所需 ... 亞甲藍氯化物(Methylthioninium Chloride). 腎功能測定、尿道消毒 ... Better Health Channel. [2011-07
GABA receptors contain a binding site for the chemical, GABA, a chloride ion channel, and an additional binding site for ... When a GABA molecule attaches to its binding site, it activates the receptor, resulting in an inflow of chloride ions. The ... When alcohol molecules bind to its site on the GABA receptor, they lengthen the time that the receptor's chloride ion pore ...
calcium chloride, ammonium chloride 1. Arginine vasopressin. receptor 2 antagonists amphotericin B, lithium[13][14]. Inhibits ... Epithelial sodium channel blockers: amiloride and triamterene.. Calcium-sparing diureticsEdit. The term "calcium-sparing ... Inhibition of Na+/K+ exchanger: Spironolactone inhibits aldosterone action, Amiloride inhibits epithelial sodium channels[17]. ... Aldosterone normally adds sodium channels in the principal cells of the collecting duct and late distal tubule of the nephron. ...
... reduction of nitro blue tetrazolium chloride, assays of chemotaxis, bactericidal activity. Due to the rarity of many primary ... deficiency CD3γ deficiency CD8 deficiency ZAP-70 deficiency Ca++ channel deficiency MHC class I deficiency MHC class II ...
More water-soluble gases (e.g. chlorine, ammonia, sulfur dioxide, hydrogen chloride) dissolve in the upper airway and ... Others modulate the activity of ion channels that control fluid transport across lung membranes or target surfactant, a ... Smoke, chlorine, phosgene, sulfur dioxide, hydrogen chloride, hydrogen sulfide, nitrogen dioxide, ozone, and ammonia are common ... hydrogen chloride, hydrogen sulfide, nitrogen dioxide, ozone, and ammonia are among the most important irritant gases. Hydrogen ...
Phenacyl chloride. *Polygodial (Dorrigo pepper). *Shogaols (ginger, Sichuan and melegueta peppers). *Tear gases ... See also: Receptor/signaling modulators • Ion channel modulators. Retrieved from "https://en.wikipedia.org/w/index.php?title= ...
... usually ensured by the Ourcq channel and by the de la Dhuis aqueduct, forced the authorities to pump water directly from the ... grenade based on chloropicrin and Fourneau discovered the chemical reaction that led to the formation of methylarsine chloride ...
Plastics: High-density polyethylene (HDPE) is compatible but polyvinyl chloride (PVC) is slowly degraded.[5] Polystyrene is ... The hand-sized square piece of metal contains microscopic channels with catalytic sites, which continuously convert biodiesel, ...
This can give rise to elevated concentrations of sodium, chloride, magnesium and sulfate as well as many other compounds in ... which underlies many larger rivers and can contain substantially more water than is seen in the open channel. It may also be in ...
Ji, Jianguo; Bunnelle, William H.; Anderson, David J.; Faltynek, Connie; Dyhring, Tino; Ahring, Philip K.; Rueter, Lynne E.; Curzon, Peter; Buckley, Michael J.; Marsh, Kennan C.; Kempf-Grote, Anita; Meyer, Michael D. (2007). "A-366833: A novel nicotinonitrile-substituted 3,6-diazabicyclo[3.2.0]-heptane α4β2 nicotinic acetylcholine receptor selective agonist: Synthesis, analgesic efficacy and tolerability profile in animal models". Biochemical Pharmacology. 74 (8): 1253-1262. doi:10.1016/j.bcp.2007.08.010. PMID 17854775 ...
Reconstitution with sodium chloride should be avoided due to formation of precipitates. Intravenous solutions of pentamidine ... L-Type calcium channel blockers (e.g., dihydropyridines: nifedipine). *Nebivolol (beta blocker) ...
This symporter is a channel responsible for the transport of multiple electrolytes such as sodium, chloride, calcium, magnesium ... channel (ClC-Kb), and the Na+/K+-ATPase. Indicated also are the recently identified magnesium channel TRPM6 in the apical ... Sodium chloride (NaCl) enters the cell via the apical thiazide-sensitive NCC and leaves the cell through the basolateral Cl− ... When the sodium-chloride cotransporter is inactivated, continued action of the basolateral Na+/K+-ATPase creates a favorable ...
... (DDE) is a chemical compound formed by the loss of hydrogen chloride (dehydrohalogenation) ... DDE concentration and percent eggshell thinning in Double-crested Conmorant eggs(North Channel, Lake Huron, Ont.) ...
They form in the presence of water at low temperatures and pressures, and have channels and voids in their structure. Zeolites ... a chloride, or an oxide ion.[112] Because of the variable chemistry, there are over 80 species of amphibole, although ...
Vending of common salt (sodium chloride) was historically a natural monopoly. Until recently, a combination of strong sunshine ... Firstly, it convinced independent producers to join its single channel monopoly, it flooded the market with diamonds similar to ... Canada and Australia to distribute diamonds outside the De Beers channel, as well as rising awareness of blood diamonds that ...
Open-channel flow measurement[edit]. Open channel flow describes cases where flowing liquid has a top surface open to the air; ... Fluorescent chloride sensors. *Holographic sensor. *Hydrocarbon dew point analyzer. *Hydrogen sensor. *Hydrogen sulfide sensor ... Wetted area velocity sensors have to be typically mounted on the bottom of a channel or river and use Doppler to measure the ... Non-contact devices that use laser or radar are mounted above the channel and measure the velocity from above and then use ...
The sodium nickel chloride or "Zebra" battery uses a molten sodium chloroaluminate (NaAlCl4) salt as the electrolyte. A ... "Car Companies' Head-on Competition In Electric Vehicle Charging." (Website). The Auto Channel, 1998-11-24. Retrieved on 2007- ... and sodium nickel chloride ("zebra") batteries.[1] The amount of electricity (i.e. electric charge) stored in batteries is ...
The membrane can then be analyzed on a patch clamp apparatus to determine the phenotype of the ion channels embedded in it. It ... Upon conducting experiments following a modified Hanahan protocol using calcium chloride in E.Coli, it was determined that ... Specially prepared giant spheroplasts of Gram-negative bacteria can be used to study the function of bacterial ion channels ... Santos, J. S., Lundby, A., Zazueta, C., and Montal, M. (2006) Molecular template for a voltage sensor in a novel K+ channel. I ...
chloride channel activity. • extracellular ligand-gated ion channel activity. • extracellular-glycine-gated chloride channel ... chloride channel complex. • cell junction. • dendrite. • glycinergic synapse. • integral component of postsynaptic ... chloride transport. • neuropeptide signaling pathway. • chloride transmembrane transport. • response to amino acid. • ... ion channel activity. • transmembrane signaling receptor activity. Cellular component. • integral component of membrane. • ...
... but could relate to actions of the drug on voltage-activated calcium channels. Lamotrigine blocks T-type calcium channels ... Lithium (lithium acetate, lithium carbonate, lithium chloride, lithium citrate, lithium hydroxide, lithium orotate) ... Ion channel blockers. *Anticonvulsants (e.g., gabapentin, pregabalin, carbamazepine, oxcarbazepine, lacosamide, lamotrigine) ... Lamotrigine is a member of the sodium channel blocking class of antiepileptic drugs.[60] This may suppress the release of ...
regulation of intracellular calcium activated chloride channel activity. • negative regulation of dendritic spine maintenance. ... ion channel binding. • microtubule binding. • ATP-dependent protein binding. • metal ion binding. • tubulin binding. • protein ...
... "channels" that can accommodate variable amounts of water, or other small molecules such as methanol. ... chloride, which functions as a moisture indicator. ...
Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many ... The chloride channel subunits contain between 1 and 12 transmembrane segments. Some chloride channels are activated only by ... Based on sequence homology the chloride channels can be subdivided into a number of groups. Voltage-gated chloride channels are ... CLC chloride channels As of this edit, this article uses content from "1.A.13 The Epithelial Chloride Channel (E-ClC) Family", ...
The chloride permeability defect which characterizes the apical membrane of secretory epithelial cells in cystic fibrosis has ... This channel is closely similar or identical to the outwardly rectifying chloride channel identified by patch clamp recording ... Cystic Fibrosis Chloride Channel Calcium Ionophore Patch Clamp Recording Secretory Epithelial Cell These keywords were added by ... Welsh, M.J., 1986, An apical-membrane chloride channel in human tracheal epithelium, Science, 23 2:1648.CrossRefGoogle Scholar ...
Identification and characterization of two histamine-gated chloride channels in the visual system of Papilio; both channels ...
Structurally, three classes of Cl- channels have been identified: ligand-gated, postsynaptic Cl- channels (e.g. GABA and ... channel and its emergent role as a regulator of other channels, clarification of issues related to swelling-activated Cl- ... channels. Recent developments of note include further characterization of the expanding CLC Cl- channel family, advances in ... Plasma membrane Cl- channels perform a variety of functions, including control of excitability in neurons and muscle, cell ...
... Clc chloride channel Identifiers Symbol Voltage_CLC Pfam PF00654 InterPro IPR014743 SCOP 1kpl TCDB 1.A.11 OPM ... The structure of these channels are not like other known channels. Chloride channel subunits contain between 1 and 12 ... Membrane transport protein: ion channels. Ca2+: Calcium channel. Voltage-dependent calcium channel (L-type/Cavα(1.1, 1.2, 1.3, ... Chloride channels are important for setting cell resting membrane potential and maintaining proper cell volume. These channels ...
... though slowly converging on a connection between single-channel activity and the identity of the mitochondrial chloride channel ... Subsequently, several types of ion channels permeable to chloride and other anions were found in the mitochondria of different ... This uncertainty was slightly reduced by two different studies: experiments that showed a significant role of chloride channels ... Our recently published single-channel electrophysiological experiments are well in line with the channel activity of ...
Rattus norvegicus chloride channel accessory 1 (Clca1), mRNA Rattus norvegicus chloride channel accessory 1 (Clca1), mRNA. gi, ... Rattus norvegicus chloride channel accessory 1 (Clca1), mRNA. NCBI Reference Sequence: NM_001107449.1 ... See the reference protein sequence for calcium-activated chloride channel regulator 1 precursor (NP_001100919.1). ... Stimuli-sensing channels Stimuli-sensing channelscomputationally inferred pathway (not manually curated) ... [bsid1376737] ...
ClC channels conduct chloride (Cl-) ions across cell membranes and thereby govern the electrical activity of muscle cells and ... The structural basis of ClC channel gating was studied. Crystal structures of wild-type and mutant Escherichia coliClC channels ... Mutations of this glutamate residue in Torpedo ray ClC channels alter gating in electrophysiological assays. These findings ...
Structure of a CLC chloride ion channel by cryo-electron microscopy.. Park E1, Campbell EB1, MacKinnon R1. ... Two soft masks were used (also see c): one (red) including only the channel portion and the other (blue) including the channel ... The extracellular features of the CLC-K channel. A domain connecting αK and αM is shown in green. In the native channel, the ... Cryo-EM density map (c) and model (d) of the CLC-K channel (Class 1). Blue and cyan, two subunits of the CLC-K homodimer. Grey ...
Variomics Screen Identifies the Re-entrant Loop of the Calcium-activated Chloride Channel ANO1 That Facilitates Channel ... 1992) Chloride channels in the apical membrane of normal and cystic fibrosis airway and intestinal epithelia. Am J Physiol 263: ... Calcium-activated chloride channels have been implicated for the STIC and also the plateau phase of depolarization in the slow ... Studies on expression and function of the TMEM16A calcium-activated chloride channel. Fen Huang, Jason R. Rock, Brian D. Harfe ...
Potassium Channel KcsA-Fab complex in Sodium Chloride. *DOI: 10.2210/pdb2ITC/pdb ... Voltage-gated potassium channel. C. 124. Streptomyces lividans. Mutation(s): 1 Gene Names: kcsA, skc1. ... Structural and Thermodynamic Properties of Selective Ion Binding in a K(+) Channel.. Lockless, S.W., Zhou, M., Mackinnon, R.. ( ... We conclude that ion selectivity in a K(+) channel is a property of size-matched ion binding sites created by the protein ...
Compare chloride channel 6 ELISA Kits from leading suppliers on Biocompare. View specifications, prices, citations, reviews, ... Bovine Chloride intracellular channel protein 6 (CLIC6) ELISA Kit MyBioSource.com *Detection Target: Chloride intracellular ... Canine Chloride intracellular channel protein 6 (CLIC6) ELISA Kit MyBioSource.com *Detection Target: Chloride intracellular ... Goat Chloride intracellular channel protein 6 (CLIC6) ELISA Kit MyBioSource.com *Detection Target: Chloride intracellular ...
Compare chloride channel 6 ELISA Kits from leading suppliers on Biocompare. View specifications, prices, citations, reviews, ... chloride channel 6 ELISA Kits. The ELISA (enzyme-linked immunosorbent assay) is a well-established antibody-based tool for ... Your search returned 23 chloride channel 6 ELISA ELISA Kit across 1 supplier. ...
Retrieved from "https://www.biology-online.org/dictionary/index.php?title=Chloride_channels&oldid=14859" ...
Belongs to the chloride channel (TC 2.A.49) family. [View classification]UniRule annotation. Automatic assertion according to ... tr,Q3TTA5,Q3TTA5_MOUSE Chloride channel protein (Fragment) OS=Mus musculus OX=10090 GN=Clcn1 PE=1 SV=1 ...
May be involved in mediating calcium-activated chloride conductance (PubMed:8537359). May play critical roles in goblet cell ... Calcium-activated chloride channel. Epithelial chloride channel protein1 Publication. ,p>Manually curated information that is ... Calcium-activated chloride channel regulator 1Add BLAST. 882. Amino acid modifications. Feature key. Position(s). Description ... Calcium-activated chloride channel regulator 1Curated (EC:3.4.-.-By similarity. ,p>Manually curated information which has been ...
... chloride channels. GABA-A receptor agonists (e.g. lorazepam) may also be considered chloride channel openers Chloride channel ... A chloride channel opener is a type of drug which facilitates ion transmission through chloride channels. An example is 1,10- ... Duszyk M, MacVinish L, Cuthbert AW (October 2001). "Phenanthrolines--a new class of CFTR chloride channel openers". British ... Cuthbert AW (February 2001). "Assessment of CFTR chloride channel openers in intact normal and cystic fibrosis murine epithelia ...
A chloride channel blocker is a type of drug which inhibits the transmission of ions (Cl−) through chloride channels. Niflumic ... Chloride channel opener Knauf PA, Mann NA (May 1984). "Use of niflumic acid to determine the nature of the asymmetry of the ... Liu J, Lai ZF, Wang XD, Tokutomi N, Nishi K (April 1998). "Inhibition of sodium current by chloride channel blocker 4,4- ... Another example is anthracene-9-carboxylic acid, a potent blocker of the CLCN1-type chloride channel found in skeletal muscle, ...
The mutations in the CLCNKB gene encoding the ClC-Kb chloride channel are responsible for Bartter syndrome type 3, one of the ... Keywords: Bartter syndrome; CLC family of chloride transporters and channels; chloride channel. ... ClC-K chloride channels: emerging pathophysiology of Bartter syndrome type 3 Am J Physiol Renal Physiol. 2015 Jun 15;308(12): ... The mutations in the CLCNKB gene encoding the ClC-Kb chloride channel are responsible for Bartter syndrome type 3, one of the ...
IPR013642 Calcium-activated chloride channel, N-terminal. IPR004727 Calcium-activated chloride channel protein, chordata ...
... Nature. 1989 Sep 21;341(6239): ... channels in alpha 2 cells. These observations provide a model for feedback regulation of glucagon release, which may be of ...
Development and validation of a potent and specific inhibitor for the CLC-2 chloride channel. View ORCID ProfileAnna K. Koster ... CLC-2 is a voltage-gated chloride channel that is widely expressed in mammalian tissues. In the central nervous system, CLC-2 ... Development and validation of a potent and specific inhibitor for the CLC-2 chloride channel ... Development and validation of a potent and specific inhibitor for the CLC-2 chloride channel ...
It has only recently emerged that several patients harbor a mutation in the gene for the ClC-2 chloride channel. ... Chloride channel continuously open. We have seen how the channel is constantly open due to these mutations, which greatly ... We have been able to show step by step what exactly happens in the organism due to the mutated chloride channel in our model ... Gene mutations in the ClC-2 chloride channel cause high blood pressure, kidney damage. *Download PDF Copy ...
J:51917 Matsumura Y, et al., Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel [see comments]. ...
MDC »Molekulare Pharmakologie »aldosterone »blood pressure »chloride »chloride channel »high blood pressure »mouse model » ... Further reports about: , MDC , Molekulare Pharmakologie , aldosterone , blood pressure , chloride , chloride channel , high ... Chloride channel continuously open. "We have seen how the channel is constantly open due to these mutations, which greatly ... "We have been able to show step by step what exactly happens in the organism due to the mutated chloride channel in our model ...
... chloride intracellular channel 4), Authors: Velayuthan C Padmakumar, Stuart H Yuspa. Published in: Atlas Genet Cytogenet Oncol ... angiogenesis endothelial cell morphogenesis voltage-gated ion channel activity chloride channel activity protein binding ... angiogenesis endothelial cell morphogenesis voltage-gated ion channel activity chloride channel activity protein binding ... CLIC4 (chloride intracellular channel 4). Written. 2009-07. Velayuthan C Padmakumar, Stuart H Yuspa. ...
Synonyms: 5430408K11Rik, Chloride channel protein 5, Chloride transporter ClC-5, ClC-5, Clc5, ... ... The loss of the chloride channel, ClC-5, delays apical iodide efflux and induces a euthyroid goiter in the mouse thyroid gland. ... Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules. ... The ClC-5 chloride channel knock-out mouse - an animal model for Dents disease. Günther, W., Piwon, N., Jentsch, T.J. Pflugers ...
This chloride channel is probably responsible for electrogenic chloride secretion by the gastric mucosa and may also ... Activation of apical chloride channels in the gastric oxyntic cell Message Subject. (Your Name) has forwarded a page to you ... A single class of voltage-dependent, inwardly rectifying chloride channels was observed in the apical membranes of both resting ... analogous to the chloride channels found in the apical membranes of other exocrine cells. ...
... involving passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism. ... Catalysis of facilitated diffusion of a chloride (by an energy-independent process) ... TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. * Alpha-aminoazaheterocyclic- ... Extracellular recording of glycine receptor chloride channel activity as a prototype for biohybrid s… ...
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  • The proteins are formed from two copies of the same protein-a homodimer-though scientists have artificially combined subunits from different channels to form heterodimers. (wikipedia.org)
  • In the exchangers, these chloride ions do not interact strongly with one another, due to compensating interactions with the protein. (wikipedia.org)
  • In the channels, the protein does not shield chloride ions at one binding site from the neighboring negatively charged chlorides. (wikipedia.org)
  • Gluex also serves to regulate chloride exchange between the protein and extracellular solution. (wikipedia.org)
  • The results are taken as strong evidence that the Cl- channel is constructed as a functional dimer of identical protein subunits. (pnas.org)
  • The experimental evidence seems to be inevitably, though slowly converging on a connection between single-channel activity and the identity of the mitochondrial chloride channel protein. (intechopen.com)
  • See the reference protein sequence for calcium-activated chloride channel regulator 1 precursor (NP_001100919.1). (nih.gov)
  • We conclude that ion selectivity in a K(+) channel is a property of size-matched ion binding sites created by the protein structure. (rcsb.org)
  • Zusätzlich bieten wir Ihnen Chloride Channel, Nucleotide-Sensitive, 1A Proteine (9) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
  • The protein is also found associated with the plasma membrane where it functions as a chloride current regulator. (antikoerper-online.de)
  • Zhang CH, Li Y, Zhao W, Lifshitz LM, Li H, Harfe BD, Zhu MS, ZhuGe R. The transmembrane protein 16A Ca(2+)-activated Cl- channel in airway smooth muscle contributes to airway hyperresponsiveness. (umassmed.edu)
  • The mechanism of S1P-induced activation of the chloride current involved Rho GTPase but not Rho-associated protein kinase. (frontiersin.org)
  • Recent achievements in the development of genetically encoded chloride probes are based on the fact that yellow fluorescent protein (YFP) exhibits Cl − -sensitivity. (frontiersin.org)
  • Patients with CF lack adequate levels of the CFTR protein, a chloride channel which is required for normal function of the lung, pancreas, liver and other organs. (bio-medicine.org)
  • The multicenter, randomized, open-label Phase 2a study demonstrated that treatment with PTC124 caused improvements in CFTR-mediated chloride conductance and in apical expression of CFTR protein in nasal epithelium. (bio-medicine.org)
  • Egan, Defective regulation of outwardly rectifying Cl- channels by protein kinase A corrected by insertion of CFTR. (xenbase.org)
  • The calcium-activated chloride channel TMEM16A is a member of a conserved protein family that comprises ion channels and lipid scramblases. (elifesciences.org)
  • 1] The ABC protein turned chloride channel whose failure causes cystic fibrosis. (axonmedchem.com)
  • The chimera, however, maintains mBest2-like pore properties, strongly indicating that the Bestrophin protein forms the \(Cl_{swell}\) channel itself rather than functioning as an essential auxiliary subunit. (harvard.edu)
  • Cytoplasmic domains in eukaryotic ClC proteins have been shown to be crucial for protein function and to be involved in the functional regulation of chloride transport. (uzh.ch)
  • the protein localizes principally to the cell nucleus and exhibits both nuclear and plasma membrane chloride ion channel activity. (creativebiomart.net)
  • The chloride channel and drug transport activities of P-glycoprotein appear to reflect two distinct functional states of the protein that can be interconverted by changes in tonicity. (cfgenetherapy.org.uk)
  • The transport and channel functions of P-glycoprotein have been separated by directed mutations in the nucleotide-binding domains of the protein. (cfgenetherapy.org.uk)
  • This dimerization domain is important for channel assembly in eukaryotic cells, and the in vitro association of peptides containing the dimerization domain is consistent with a homotypic protein-protein interaction. (escholarship.org)
  • We have now demonstrated that the surface channels are rapidly internalised and approximately the 70% of the surface membrane protein recycles after 4- to 8-min internalisation. (semanticscholar.org)
  • These two proteins belong to, respectively, the CLC and ABC transport protein families whose members encompass both ion channels and transporters. (elsevier.com)
  • Furthermore, the joined force between structural and functional studies of these two protein families has offered a unique opportunity to peek into the evolutionary link between ion channels and transporters. (elsevier.com)
  • Recent developments of note include further characterization of the expanding CLC Cl- channel family, advances in understanding the regulation of the CFTR Cl- channel and its emergent role as a regulator of other channels, clarification of issues related to swelling-activated Cl- channels, and the discovery that several co-transporter molecules are now known to induce Cl- currents in Xenopus oocytes. (mdc-berlin.de)
  • An example is 1,10-phenanthroline, which activates Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels. (wikipedia.org)
  • The cystic fibrosis transmembrane conductance regulator (CFTR) is a phosphorylation- and ATP-dependent chloride channel that modulates salt and water transport across lung and gut epithelia. (rupress.org)
  • Here we show that CFTR channel activity in excised membrane patches is markedly inhibited by several oxidized forms of glutathione (i.e. (rupress.org)
  • At the single channel level, the primary effect of reactive glutathione species was to markedly inhibit the opening rates of individual CFTR channels. (rupress.org)
  • CFTR channel inhibition was not obviously dependent on phosphorylation state but was markedly slowed when channels were first "locked open" by a poorly hydrolyzable ATP analogue (AMP-PNP). (rupress.org)
  • Our results demonstrate that human CFTR channels are reversibly inhibited by reactive glutathione species, and support an important role of the region proximal to the NBD2 signature sequence in ATP-dependent channel opening. (rupress.org)
  • Current models of CFTR channel gating (e.g. (rupress.org)
  • Whether the two CFTR NBDs also associate to form composite ATP binding sites, and how nucleotide binding subsequently promotes CFTR channel opening, are unresolved issues. (rupress.org)
  • CFTR channels potentially can be modulated by oxidants in addition to the more well-studied physiologic activators (e.g. (rupress.org)
  • Cellular distribution of cystic fibrosis transmembrane conductance regulator (CFTR) immunofluorescence was detected by monoclonal antibody directed to the C terminus of killifish CFTR (kfCFTR) in chloride cells of fresh water (FW) adapted fish and animals transferred to sea water (SW) for 24h, 48h and 14+ days. (biologists.org)
  • CFTR, the anion channel responsible for Cl - secretion in marine teleosts, redistributes in MR cells during SW acclimation by condensation of a diffuse distribution below the apical crypt, followed by translocation and insertion in the apical membrane. (biologists.org)
  • Ion channels and transporters (i.e. cystic fibrosis transmembrane regulator (CFTR), inward rectifier potassium channel (eKir), Na/K-ATPase, Na/K/Cl2 co-transporter (NKCC), aquaporin-3 (AQP-3), and Na/H exchanger-1 (NHE-1)) are known to be expressed in gill epithelia of teleost fish. (unboundmedicine.com)
  • Across a variety of studies, TEPD assessments showed statistically significant improvements of mean CFTR-dependent chloride secretion in the airways. (bio-medicine.org)
  • PTC124 also induced significantly improved CFTR-mediated chloride channel activity as measured by nasal potential difference, with 40 percent of patients achieving values in the normal range during PTC124 administration. (bio-medicine.org)
  • Chloride channel and chloride conductance regulator domains of CFTR , the cystic fibrosis transmembrane conductance regulator. (xenbase.org)
  • CFTR is a cyclic AMP (cAMP)-activated chloride (Cl-) channel and a regulator of outwardly rectifying Cl- channels (ORCCs) in airway epithelia. (xenbase.org)
  • To define the domains of CFTR important for Cl- channel function and/or ORCC regulator function, mutant CFTRs with N- and C-terminal truncations and selected individual amino acid substitutions were created and studied by transfection into a line of human airway epithelial cells from a cystic fibrosis patient (IB3-1) or by injection of in vitro transcribed complementary RNAs (cRNAs) into Xenopus oocytes. (xenbase.org)
  • Two-electrode voltage clamp recordings, 36Cl- efflux assays, and whole cell patch-clamp recordings were used to assay for the Cl- channel function of CFTR and for its ability to regulate ORCCs. (xenbase.org)
  • The data showed that the first transmembrane domain ( TMD -1) of CFTR , especially predicted alpha-helices 5 and 6, forms an essential part of the Cl- channel pore, whereas the first nucleotide-binding and regulatory domains (NBD1/R domain) are essential for its ability to regulate ORCCs. (xenbase.org)
  • Gabriel, CFTR and outward rectifying chloride channels are distinct proteins with a regulatory relationship. (xenbase.org)
  • Like the P2X receptors , the CFTR has an ATP binding domain, and is considered a cAMP-activated ATP-gated anion channel. (axonmedchem.com)
  • Chloride transport through the CFTR channel works in concert with sodium transport through epithelial sodium channels (ENaC) to maintain salt, fluid, and pH homeostasis in various epithelial tissues. (axonmedchem.com)
  • The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride ion channel whose defects cause the deadly genetic disease cystic fibrosis (CF). Like other ATP binding cassette (ABC) proteins, CFTR encompasses two cytoplasmic nucleotide binding domains (NBDs). (umsystem.edu)
  • Moreover, I discovered several mutations that enhance ATP binding in site 1 and demonstrated that the activity of CF-associated mutant channels, ΔF508- and G551D-CFTR, can be significantly improved by these mutations, thus providing evidence that site 1 is a potential target for developing pharmaceutical reagents to treat patients with CF. (umsystem.edu)
  • The cystic fibrosis transmembrane conductance regulator (CFTR) was expressed in cultured cystic fibrosis airway epithelial cells and Cl- channel activation assessed in single cells using a fluorescence microscopic assay and the patch-clamp technique. (centerforfacialappearances.com)
  • Expression of CFTR, but not of a mutant form of CFTR (delta F508), corrected the Cl- channel defect. (centerforfacialappearances.com)
  • CFTR is located in the apical membranes of many secretory epithelia and is associated with a cyclic AMP-regulated chloride channel. (cfgenetherapy.org.uk)
  • Because of the structural and sequence similarities between P-glycoprotein and CFTR, and because P-glycoprotein is abundant in many secretory epithelia, we examined whether P-glycoprotein might be associated with one or other of these channels. (cfgenetherapy.org.uk)
  • The wine extract did not inhibit the cystic fibrosis chloride channel (CFTR) in cell cultures, nor did it prevent watery stools in neonatal mice administered cholera toxin, which activates CFTR-dependent fluid secretion. (bmj.com)
  • CLC-0 and cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channels play important roles in Cl - transport across cell membranes. (elsevier.com)
  • CLC-0 and CFTR can be considered operationally as ligand-gated channels, though binding of the activating ligands appears to be coupled to an irreversible gating cycle driven by an input of free energy. (elsevier.com)
  • High-resolution crystallographic structures of bacterial CLC proteins and ABC transporters have led us to a better understanding of the gating properties for CLC and CFTR Cl - channels. (elsevier.com)
  • Chen, T-Y & Hwang, TC 2008, ' CLC-0 and CFTR: Chloride channels evolved from transporters ', Physiological Reviews , vol. 88, no. 2, pp. 351-387. (elsevier.com)
  • As we describe here, transformed lympho-blasts have whole cell chloride currents under conditions of stimulation by cAMP agonists, calcium ionophore, or hypotonicity which are quite similar to the aggregate chloride currents measured under similar conditions in epithelial cells. (springer.com)
  • The genetically modified mice exhibited enormously increased chloride currents in aldosterone-secreting cells, which indirectly led to a large increase in aldosterone concentration in the blood of those rodents. (news-medical.net)
  • Inhibition of vascular calcium-gated chloride currents by blockers of KCa1.1, but not by modulators of KCa2.1 or KCa2.3 channels. (sigmaaldrich.com)
  • The goal of the present study was to ascertain whether blockers of K(Ca)1.1 inhibited calcium-activated Cl(-) currents (I(ClCa)) and if the pharmacological overlap between K(Ca)1.1 and CaCCs extends to intermediate and small conductance, calcium-activated K(+) channels. (sigmaaldrich.com)
  • Fulmer, Two cystic fibrosis transmembrane conductance regulator mutations have different effects on both pulmonary phenotype and regulation of outwardly rectified chloride currents. (xenbase.org)
  • 1.The cell-volume regulation by chloride currents was studied in guinea-pig cardiac myocytes, using a microscopic video-image analysis. (nii.ac.jp)
  • In addition, we characterise the chloride currents in hBECs and determine how inhibition of CLIC1 via pharmacological and molecular approaches impacts these. (nottingham.ac.uk)
  • We demonstrate that CLIC1 is able to modulate cyclic AMP-induced chloride currents and suggest that CLIC1 modulation could be important for chloride homeostasis in this cell type. (nottingham.ac.uk)
  • This uncertainty was slightly reduced by two different studies: experiments that showed a significant role of chloride channels in the process of mitochondrial membrane potential oscillations and experiments that localized chloride intracellular ion channel (CLIC) proteins in cardiac mitochondrial membranes. (intechopen.com)
  • Our recently published single-channel electrophysiological experiments are well in line with the channel activity of recombinant CLIC proteins. (intechopen.com)
  • The results from these different fields of research are discussed and combined to identify a connection between measured chloride channel activities and the identity of the corresponding proteins. (intechopen.com)
  • CLC proteins transport chloride (Cl - ) ions across cellular membranes to regulate muscle excitability, electrolyte movement across epithelia, and acidification of intracellular organelles. (nih.gov)
  • Some CLC proteins are channels that conduct Cl - ions passively, whereas others are secondary active transporters that exchange two Cl - ions for one H + . The structural basis underlying these distinctive transport mechanisms is puzzling because CLC channels and transporters are expected to share the same architecture on the basis of sequence homology. (nih.gov)
  • CLC proteins come in two flavors: anion channels and anion/proton exchangers. (mdc-berlin.de)
  • ClC-1 is member of the ClC family of anion channels and transporters, a large family of anion transport proteins with many unique properties ( Jentsch, 2008 ), and studies on ClC-1 contributed significantly to our understanding of this class of transport proteins. (rupress.org)
  • The chloride channel (CLC) family of Cl − transport proteins includes both Cl − channels and proton-coupled Cl − exchange transporters ( Zifarelli & Pusch 2007 ). (royalsocietypublishing.org)
  • However, some TMEM16 proteins transport ions in or out of the cell, and are instead called ion channels. (elifesciences.org)
  • It also gives insight into how TMEM16 proteins might work as ion channels. (elifesciences.org)
  • The voltage-dependent chloride channel (CLC) family of membrane proteins has cognates in animals, yeast, bacteria and plants, and chloride-channel activity has been assigned to most of the animal homologues. (biochemj.org)
  • Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. (creativebiomart.net)
  • Ion channels and transporters were traditionally viewed as distinct entities in membrane transport physiology, but recent discoveries have blurred the line between these two classes of membrane transport proteins. (elsevier.com)
  • Calcium-activated chloride channels (CaCC) with similar hallmark features are present in many cell types and mediate important physiological functions including epithelial secretion, sensory signal transduction, and smooth muscle contraction. (pnas.org)
  • We now describe a mechanism whereby GABA, co-secreted with insulin from beta cells, may mediate part of the inhibitory action of glucose on glucagon secretion by activating GABAA-receptor Cl- channels in alpha 2 cells. (nih.gov)
  • Patch-clamp techniques were applied to these cells to identify apical membrane ion channels associated with hydrochloric acid secretion. (sciencemag.org)
  • This chloride channel is probably responsible for electrogenic chloride secretion by the gastric mucosa and may also participate in the fluid- and enzyme-secretory functions of the oxyntic cell, analogous to the chloride channels found in the apical membranes of other exocrine cells. (sciencemag.org)
  • Mitochondria-rich chloride (MR) cells of the skin and gill epithelia of teleost fish are responsible for ion uptake in fresh water (FW) teleosts fish (for a review, see Perry, 1997 ) and ion secretion in sea water (SW) teleosts (for a review, see Marshall and Bryson, 1998 ). (biologists.org)
  • Chloride secretion in skin and gill epithelia of SW-adapted teleosts is localized to the apical crypts of exposed MR cells ( Foskett and Scheffey, 1982 ). (biologists.org)
  • Chloride channel activity at the apical membrane determines the rate and direction of salt and water secretion. (deepdyve.com)
  • K + channel blockade was measured by the inhibition of chloride secretion resulting from depolarization. (aspetjournals.org)
  • However, when 1-ethyl-2-benzimidazolinone (EBIO) was used to stimulate chloride secretion, XE991 was ineffective unless charybdotoxin was also present. (aspetjournals.org)
  • Activation or inhibition of K + channels in epithelia, particularly those secreting chloride, has potentially useful therapeutic applications in diseases as diverse as cystic fibrosis, where chloride secretion is deficient, and secretory diarrhea, where it is in excess. (aspetjournals.org)
  • Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction. (axonmedchem.com)
  • K+ and Cl- channels and transporters in sperm function. (umassmed.edu)
  • This region is predicted to participate in ATP-dependent channel opening and to be occluded in the nucleotide-bound state of the channel based on structural comparisons to related ATP binding cassette transporters. (rupress.org)
  • The concentration of intracellular Cl − and its permeance is highly regulated by a variety of Cl − -selective channels and Cl − transporters (revs. (frontiersin.org)
  • The present study is the first to demonstrate the activation of the mRNA transcripts for the ion channels and transporters in isolated gill CCs during seawater acclimation. (unboundmedicine.com)
  • ClC chloride channels and transporters catalyze the selective flow of chloride ions across the membranes of prokaryotic and eukaryotic cells. (uzh.ch)
  • This information will serve as the structural basis for future investigations that may reveal the mechanisms of regulation by the cytoplasmic domains in ClC chloride channels and transporters. (uzh.ch)
  • A gene on chromosome Xp11.23-p11.22 that encodes a member of the voltage-gated chloride channel and ion transporters. (thefreedictionary.com)
  • Cell biology and physiology of CLC chloride channels and transporters. (semanticscholar.org)
  • The inhibition by 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS) of Cl- channels from Torpedo electroplax incorporated in planar phospholipid bilayer membranes is studied. (pnas.org)
  • Chloride channel inhibition blocks the protection of ischemic preconditioning and hypo-osmotic stress in rabbit ventricular myocardium. (ahajournals.org)
  • Chloride channel inhibition does block the protection of ischemic preconditioning in myocardium. (ahajournals.org)
  • 2]. Mutations in the human skeletal muscle chloride channel gene (CLCN1) associated with dominant and recessive myotonia congenita. (bionity.com)
  • Mutations of this glutamate residue in Torpedo ray ClC channels alter gating in electrophysiological assays. (sciencemag.org)
  • The mutations in the CLCNKB gene encoding the ClC-Kb chloride channel are responsible for Bartter syndrome type 3, one of the four variants of Bartter syndrome in the genetically based nomenclature. (nih.gov)
  • This review provides an overview of recent progress in the functional consequences of CLCNKB mutations on ClC-Kb chloride channel activity. (nih.gov)
  • Although further investigation is needed to fully characterize disease pathogenesis, Bartter syndrome type 3 probably belongs to the large family of conformational diseases, in which the mutations destabilize channel structure, inducing ClC-Kb retention in the endoplasmic reticulum and accelerated channel degradation. (nih.gov)
  • In 2018, Paris-based scientists around Prof. Maria-Christina Zennaro teamed up with colleagues from the Leibniz-Forschungsinstitut fuer Molekulare Pharmakologie (FMP) and the Max Delbrueck Center (MDC) as well as other scientists in Germany and the USA around Prof. Ute Scholl from the Berlin Institute of Health (BIH) and Charite, and found mutations in the ClC-2 chloride channel in patients affected by this syndrome. (news-medical.net)
  • The team, led by Prof. Thomas Jentsch - a pioneer who discovered the first chloride channel family, including ClC-2, almost three decades ago, initially investigated all known aldosteronism-causing ClC-2 mutations in vitro. (news-medical.net)
  • They found that all these mutations drastically increased the flow of chloride through the channel. (news-medical.net)
  • We have seen how the channel is constantly open due to these mutations, which greatly changes the electrical voltage across the membrane of the hormone-producing cell. (news-medical.net)
  • Publications] Morimoto,T et al: 'Mutations in CLCN5 chloride channel in Japanese patients with low moleailar proteinceria' J.Am.Soc.Nephrol.9. (nii.ac.jp)
  • Mutations in the ClC-1 Cl − channel cause recessive and dominant forms of this disease. (biochemj.org)
  • The Gitelman variant is uniformly caused by mutations in the gene for the thiazide-sensitive NaCl-cotransporter NCCT (SLC12A3) of the distal tubule, while HPS/aBS is caused by mutations in the gene for either the furosemide-sensitive NaK-2Cl-cotransporter NKCC2 (SLC12A1) or the inwardly rectifying potassium channel ROMK (KCNJ1) . (asnjournals.org)
  • Recently, mutations in a basolateral chloride channel CLC-Kb (CLCNKB) have been described in a subset of patients with a Bartter-like phenotype typically lacking nephrocalcinosis. (asnjournals.org)
  • This study adds 16 novel mutations to the nine already described, providing further evidence that mutations in the gene for the basolateral chloride channel CLC-Kb are the molecular basis of classic Bartter syndrome. (asnjournals.org)
  • It is caused by mutations in CLCN1 on chromosome 7q35, which alter the function of the major skeletal muscle voltage-gated chloride channel. (oup.com)
  • Our molecular expression studies of the new exon 8 mutations indicate that this region of the chloride channel has an important role in dominant negative interactions between the two chloride channel monomers. (oup.com)
  • It has only recently emerged that several patients harbor a mutation in the gene for the ClC-2 chloride channel. (news-medical.net)
  • A gene on chromosome 7q34 that encodes a voltage-gated chloride channel that regulates the electric excitability of skeletal muscle membranes. (thefreedictionary.com)
  • In the present study, we identified two CLCN voltage-gated chloride channels, CLCN3 and CLCN5, which mediated a S1P-induced excitatory Cl − current in sensory neurons by combining RNA-seq, adenovirus-based gene silencing and whole-cell electrophysiological voltage-clamp recordings. (frontiersin.org)
  • Publications] Uchida,S et al: 'Isolation and Characterization of kidney-specific CLC-K1 chloride channel gene promoter' Am.J.Physiol.274. (nii.ac.jp)
  • Publications] Matsumura.Y et al: 'Transcriptional regulation of aquaporin-2 water channel gene by CAUP' J.Am.Soc.Nephrol.8. (nii.ac.jp)
  • Isolation and characterization of kidney-specific CIC-K1 chloride channel gene promoter. (nii.ac.jp)
  • Transcriptional regulation of aquaporin-2 water channel gene by cAMP. (nii.ac.jp)
  • This gene encodes a member of the chloride intracellular channel (CLIC) family of chloride ion channels. (creativebiomart.net)
  • Publications] Kaibara, M.: 'Identification of human Kir2.2(KCNJ12) gene encoding functional inward rectifier potassium channel in both mammalian cells and Xenopus oocytes. (nii.ac.jp)
  • The detection of the stop codon in the adr(mto) allele is further indication of the identity of the Clc-1 chloride channel with the adr myotonia gene in the mouse, because a chain termination close to the N terminus would necessarily destroy gene function. (uni-bielefeld.de)
  • Another example is anthracene-9-carboxylic acid, a potent blocker of the CLCN1-type chloride channel found in skeletal muscle, which is used to study animal models of myotonia congenita. (wikipedia.org)
  • A genetic human disease, myotonia congenita, helped to clarify the impact of muscle chloride channels and provided an example of how background conductances can contribute to the modulation of cell excitability. (rupress.org)
  • Ismailov, Regulation of epithelial sodium channels by the cystic fibrosis transmembrane conductance regulator. (xenbase.org)
  • Jovov, Interaction between cystic fibrosis transmembrane conductance regulator and outwardly rectified chloride channels. (xenbase.org)
  • Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells. (centerforfacialappearances.com)
  • Ca2+-activated Cl- channels mediate physiological functions independently of cystic fibrosis transmembrane conductance regulator. (inserm.fr)
  • DIDS irreversibly and rapidly inhibits the macroscopic conductance of membranes containing many channels. (pnas.org)
  • ClC channels conduct chloride (Cl - ) ions across cell membranes and thereby govern the electrical activity of muscle cells and certain neurons, the transport of fluid and electrolytes across epithelia, and the acidification of intracellular vesicles. (sciencemag.org)
  • A single class of voltage-dependent, inwardly rectifying chloride channels was observed in the apical membranes of both resting and stimulated (acid-secreting) oxyntic cells. (sciencemag.org)
  • In mammals, ClC-1, -2, -Ka/-Kb are plasma membrane Cl(-) channels, whereas ClC-3 through ClC-7 are 2Cl(-)/H+(-exchangers in endolysosomal membranes. (mdc-berlin.de)
  • The purpose of the study was to examine the interaction of XE991 with other types of K + channel, especially those in the basolateral membranes of murine epithelia. (aspetjournals.org)
  • IIndanyloxyacetic acid-sensitive chloride channels from outer membranes of skeletal muscle", Journal of Biological Chemistry , vol. 268, 1993, pp. 547-551. (uni-bielefeld.de)
  • At the molecular level, super-resolution fluorescence imaging and Western blot analysis yielded invaluable information about the localization of chloride intracellular channel (CLIC) isoforms in the mitochondrial membrane. (intechopen.com)
  • The molecular identification of TMEM16A and TMEM16B as CaCC subunits has made it possible to examine the physiological functions of calcium-activated chloride channels in molecular and genetic studies. (pnas.org)
  • Although calcium-activated chloride channel (CaCC) flux has been described in many cell types, including human airway smooth muscle (HASM), the true molecular identity of the channels responsible for this chloride conductance remains controversial. (sigmaaldrich.com)
  • Molecular functions of anoctamin 6 (TMEM16F): a chloride channel, cation channel, or phospholipid scramblase? (springer.com)
  • The underlying molecular mechanism for the S1P-induced chloride conductance remains elusive. (frontiersin.org)
  • We investigated the molecular basis of the Cl- dependence in heterologously expressed hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that represent the molecular correlate of I(f). (unboundmedicine.com)
  • A new molecular probe has been constructed by introducing into the cytoplasmic domain of the Cl − -selective glycine receptor (GlyR) channel the CFP-YFP-based Cl-Sensor. (frontiersin.org)
  • Mutation in CLCN5 chloride channel in Japanese patients with low molecular weight proteinuria. (nii.ac.jp)
  • Despite intensive efforts to assign a molecular identity to the mammalian \(Cl_{swell}\) channel, it remains unknown. (harvard.edu)
  • Our goal is to identify the molecular candidate of the calcium-activated anion channel. (arvojournals.org)
  • Myotonic muscle fibers exhibit a decreased resting chloride conductance ( Lipicky and Bryant, 1973 ), and normal muscle fibers can be made hyperexcitable upon block of muscle chloride channels ( Bryant and Morales-Aguilera, 1971 ). (rupress.org)
  • In a landmark study on muscle excitability and myotonia, Adrian and Bryant (1974) demonstrated that the existence of transverse tubules, deep invaginations of the sarcolemma that permit the quick penetration of electrical signals to the muscle interior, makes muscle chloride channels necessary for normal muscle excitability. (rupress.org)
  • Dysfunction of muscle chloride channels in myotonia does not modify the shape of the action potential ( Lipicky and Bryant, 1973 ), and so it can be concluded that these channels do not contribute to the repolarization of the muscle fiber. (rupress.org)
  • Linking muscle chloride channels to one of the first known ion channelopathies and the identification of a role of anion channels in cellular excitability raised the interest of the ion channel community on this class of channels. (rupress.org)
  • However, for many years, muscle chloride channels resisted a detailed biophysical characterization. (rupress.org)
  • Up to now, no ligand was available for the biochemical characterization of muscle chloride channels. (uni-bielefeld.de)
  • CLCN1 is involved in setting and restoring the resting membrane potential of skeletal muscle, while other channels play important parts in solute concentration mechanisms in the kidney. (wikipedia.org)
  • The CLCN family of voltage-dependent chloride channel genes comprises nine members (CLCN1-7, Ka and Kb) which demonstrate quite diverse functional characteristics while sharing significant sequence homology. (antibodies-online.com)
  • Plasma membrane Cl- channels perform a variety of functions, including control of excitability in neurons and muscle, cell volume regulation and transepithelial transport. (mdc-berlin.de)
  • Immunofluorescence staining of the bovine CLC-K channel expressed on the plasma membrane. (nih.gov)
  • Electrophysiological studies in Chinese hamster ovary (CHO-K1) cells indicated that NCC27 chloride conductance varied according to the stage of the cell cycle, being expressed only on the plasma membrane of cells in G2/M phase. (garvan.org.au)
  • We also demonstrate that Cl- ion channel blockers known to block NCC27 led to arrest of CHO-K1 cells in the G2/M stage of the cell cycle, the same stage at which this ion channel is selectively expressed on the plasma membrane. (garvan.org.au)
  • The rotaviral enterotoxin, NSP4, has been proposed to stimulate calcium-activated chloride channels (CaCC) on the apical plasma membrane of intestinal epithelial cells. (bmj.com)
  • Among the chloride channel family members, Chloride Channel-3 (ClC-3) is believed to be located on the plasma membrane of mammalian cells, which is associated with the alterations in cell volume, and subsequently involved in the regulation of cell migration, proliferation, differentiation, and apoptosis [ 11 - 13 ]. (alliedacademies.org)
  • Rapid recycling of ClC-2 chloride channels between plasma membrane and endosomes: role of a tyrosine endocytosis motif in surface retrieval. (semanticscholar.org)
  • The TMEM16A expression pattern established in this study thus provides a roadmap for the analyses of physiological functions of calcium-activated chloride channels that contain TMEM16A subunits. (pnas.org)
  • TMEM16A is a member of the TMEM16 family that transports negatively charged chloride ions. (elifesciences.org)
  • However, because nhTMEM16 is a scramblase, not an ion channel, the location of the pore in the TMEM16A channel remains unclear. (springermedizin.de)
  • Anoctamin 1 (ANO1/TMEM16A) was identified as the major Ca2+-activated Cl- channel in airway epithelial cells, and we recently demonstrated that downregulation of the anoctamin 1 channel in cystic fibrosis patients contributes to disease severity via an unknown mechanism. (inserm.fr)
  • TMEM16A is a novel calcium-activated chloride channel first cloned in 2008. (escholarship.org)
  • This work describes two studies investigating the structure and function of TMEM16A ion channels. (escholarship.org)
  • In the first, I report a series of experiments that show that TMEM16A channels have a homodimeric architecture facilitated by its cytoplasmic N-terminus. (escholarship.org)
  • Amino acid substitutions in the dimerization domain affect functional TMEM16A-CaCC channel expression as expected from its critical role in channel subunit assembly. (escholarship.org)
  • Shikonin is a potent TMEM16A chloride channel inhibitor with an IC 50 of 6.5 μM. (medchemexpress.com)
  • Voltage-gated chloride channels display a variety of important physiological and cellular roles that include regulation of pH, volume homeostasis, organic solute transport, cell migration, cell proliferation and differentiation. (wikipedia.org)
  • Although the resting muscle chloride conductance largely exceeds the resting potassium conductance, chloride ions do not contribute to the resting membrane potential under physiological conditions. (rupress.org)
  • The physiological role of the muscle chloride conductance was therefore initially unclear. (rupress.org)
  • This review briefly discusses the main approaches for monitoring chloride (Cl − ), the most abundant physiological anion. (frontiersin.org)
  • The new genetically encoded chloride probes offer means of screening pharmacological agents, analysis of Cl − homeostasis and functions of Cl − -selective channels under different physiological and pathological conditions. (frontiersin.org)
  • Work of Christel Depienne, researcher in ICM in Alexis Brice's team with collaborators, highlight on physiological role of ClC-2 chloride channel involved in water homeostasis in white matter of humain brain. (icm-institute.org)
  • KCNQ potassium channels occur in the heart, nervous tissue, and many epithelia ( Busch and Suessbrich, 1997 ) and have important physiological functions. (aspetjournals.org)
  • Chloride channels are known to play critical physiological roles in many cell types. (nottingham.ac.uk)
  • The broad specificity of the pathway, its non-saturability in the physiological concentration range, and its failure to distinguish between stereoisomers (L- and D-alanine) are consistent with its being a type of pore or channel. (ox.ac.uk)
  • Several families of voltage-gated channels and ligand-gated channels (e.g., the CaCC families) have been characterized in humans. (wikipedia.org)
  • The plateau phase is diminished in low [Cl − ] o solution or solution containing the CaCC inhibitor DIDS, thus implicating the calcium-activated chloride current ( 17 , 18 ). (pnas.org)
  • McNicholas, Sensitivity of a renal K+ channel (ROMK2) to the inhibitory sulfonylurea compound glibenclamide is enhanced by coexpression with the ATP-binding cassette transporter cystic fibrosis transmembrane regulator. (xenbase.org)
  • TY - JOUR T1 - Characterization of ion channel and transporter mRNA expressions in isolated gill chloride and pavement cells of seawater acclimating eels. (unboundmedicine.com)
  • Characterization of [3H]ethynylbicycloorthobenzoate ([3H]EBOB) binding and the action of insecticides on the gamma-aminobutyric acid-gated chloride channel in cultured cerebellar granule neurons. (aspetjournals.org)
  • 1]. Reconstitution of functional voltage-gated chloride channels from complementary fragments of CLC-1. (bionity.com)
  • Functional expression of the TMEM16 family of calcium-activated chloride channels in airway smooth muscle. (sigmaaldrich.com)
  • Heterologous expression on channels permitted detailed functional investigation of this channel. (rupress.org)
  • Although the structure of the scramblase nhTMEM16 has defined the architecture of the family, it was unknown how a channel has adapted to cope with its distinct functional properties. (elifesciences.org)
  • Our study thus reveals the structural basis of anion conduction in a TMEM16 channel and it defines the foundation for the diverse functional behavior in the TMEM16 family. (elifesciences.org)
  • Ligand-gated chloride channels are important insecticide targets and here we highlight copy number and functional divergence in insect lineages, raising the potential that order-specific receptors could be isolated within an effective class of insecticide targets. (g3journal.org)
  • Functional, biochemical and NMR spectroscopy studies revealed that the CTD region encompasses a segment conserved in most voltage-dependent CLC channels that folds with a secondary structure containing a short type II poly-proline helix. (biochemj.org)
  • Functional Role of CLIC1 Ion Channel in Glioblastoma-Derived Stem/Progenitor Cells. (creativebiomart.net)
  • Voltage-gated Cl − channels belonging to the ClC family appear to function as homomultimers, but the number of subunits needed to form a functional channel is controversial. (rupress.org)
  • Transport of diverse substrates into malaria-infected erythrocytes via a pathway showing functional characteristics of a chloride channel. (ox.ac.uk)
  • Functionally, we demonstrate that the classic chloride channel inhibitor, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), inhibited halide flux in cultured HASM cells. (sigmaaldrich.com)
  • MTT assay showed that SIN-1 could decrease the cell viability of rat hippocampal neurons, which could be restored by the chloride channel inhibitor, DIDS (4, 4'-diisothiocyanostilbene-2, 2'- disulfonic acid). (alliedacademies.org)
  • Recent findings of TMEM16B in photoreceptor terminals ( 10 ) and olfactory neuron cilia ( 11 ) suggest that calcium-activated chloride channels containing the TMEM16B subunit likely fulfill the negative and positive feedback regulation, respectively, in these sensory neurons. (pnas.org)
  • Recent pharmacological studies have proposed there is a high degree of similarity between calcium-activated Cl(-) channels (CaCCs) and large conductance, calcium-gated K(+) channels (K(Ca)1.1). (sigmaaldrich.com)
  • However, the pharmacological overlap that exists between CaCCs and K(Ca)1.1 does not extend to the calcium-binding domain or to other calcium-gated K(+) channels. (sigmaaldrich.com)
  • Calcium activated Chloride Channels (CaCCs) are anion-selective channels that are activated by increases in cytosolic Ca 2+ . (axonmedchem.com)
  • Calcium-activated chloride channels: (un)known, (un)loved? (axonmedchem.com)
  • Using a proteomic approach, a calcium activated chloride channel, TMEM16F, was identified as candidate "flippase. (arvojournals.org)
  • Calcium activated Chloride Channel A4 (CLCA4), as a tumor suppressor, was reported to contribute to the progression of several malignant tumors, yet little is known about the significance of CLCA4 in invasion and prognosis of hepatocellular carcinoma (HCC). (readbyqxmd.com)
  • The Calcium-activated chloride channel (bCLCA1) is expressed in bovine cornea endothelial cells and may be involved in anion transport across the BCEC. (arvojournals.org)
  • The target site blocker is tested in in vitro and in mouse models of cystic fibrosis, and could be considered as an alternative strategy to treat cystic fibrosis.Downregulation of the anoctamin 1 calcium channel in airway epithelial cells contributes to pathology in cystic fibrosis. (inserm.fr)
  • Shikonin Inhibits Intestinal Calcium-Activated Chloride Channels and Prevents Rotaviral Diarrhea. (medchemexpress.com)
  • Dietary glycine prevents peptidoglycan polysaccharide-induced reactive arthritis in the rat: role for glycine-gated chloride channel. (biomedsearch.com)
  • 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. (biomedsearch.com)
  • NCC27 is a nuclear chloride ion channel, identified in the PMA-activated U937 human monocyte cell line. (garvan.org.au)
  • The chloride permeability defect which characterizes the apical membrane of secretory epithelial cells in cystic fibrosis has been difficult to study in part because of lack of accessibility of tissue for study. (springer.com)
  • This channel is closely similar or identical to the outwardly rectifying chloride channel identified by patch clamp recording from the apical membrane in secretory epithelial cells (Frizzell et al. (springer.com)
  • Stimulation of the cells with dibutyryladenosine 3',5'-monophosphate and isobutylmethylxanthine increased channel open probability and simultaneously increased apical membrane surface area. (sciencemag.org)
  • Structurally, three classes of Cl- channels have been identified: ligand-gated, postsynaptic Cl- channels (e.g. (mdc-berlin.de)
  • These ligand-gated ion channels are activated upon an increase of the intracellular Ca 2+ concentration as a consequence of cellular signaling events. (elifesciences.org)
  • Ligand-gated chloride channels have established roles in inhibitory neurotransmission in the nervous systems of vertebrates and invertebrates. (g3journal.org)
  • Paradoxically, expression databases in Drosophila melanogaster have revealed that three uncharacterized ligand-gated chloride channel subunits, CG7589, CG6927, and CG11340, are highly expressed in nonneuronal tissues. (g3journal.org)
  • The chloride channel subunits contain between 1 and 12 transmembrane segments. (wikipedia.org)
  • Each channel or exchanger is composed of two similar subunits-a dimer-each subunit containing one pore. (wikipedia.org)
  • Thus, the selectivity of the cognitive enhancer is dependent on the type of subunits colocalized with particular K + channels. (aspetjournals.org)
  • γ-aminobutyric acid (GABA)-gated chloride channel (GABA-Cl) and neuronal acetylcholine receptor (nAChR) subunits showed significantly lower transcript levels in PT lice compared to S lice. (stir.ac.uk)
  • GABA-stimulated 36 Cl − influx is completely blocked by both [ 3 H]ethynylbicycloorthobenzoate and 12-ketoendrin (two GABA-gated chloride channel blockers) and AVM B 1a at 1 to 1.5 μM. (aspetjournals.org)
  • Also, 36 Cl − influx induced by AVM B 1a at 10 nM is suppressed by the two channel blockers. (aspetjournals.org)
  • The study involved pre-incubation of rat aortic rings with potassium channels blockers: charybdotoxin (chtx), tetraethylammonium (TEA), barium chloride (BaCl2 ), glibenclamide, 4-aminopyridine (4-AP) and clotrimazole. (readbyqxmd.com)
  • Moreover, blockers of chloride channels have been shown to possess protective effects against apoptotic responses [ 8 , 10 ]. (alliedacademies.org)
  • Bao R, Lifshitz LM, Tuft RA, Bellvé K, Fogarty KE, ZhuGe R. A close association of RyRs with highly dense clusters of Ca2+-activated Cl- channels underlies the activation of STICs by Ca2+ sparks in mouse airway smooth muscle. (umassmed.edu)
  • The CLC family of chloride channels contains 10 or 12 transmembrane helices. (wikipedia.org)
  • The importance of one such group, the CLC family of chloride channels, can be seen from the diseases that develop when the channel does not function normally. (bionity.com)
  • NKCC, the cotransporter that translocates Cl - across the basolateral membrane, moves from an eccentric cytosolic location in FW to a diffuse basolateral localization in SW chloride cells. (biologists.org)
  • XE991 inhibited the chloride secretory current in colonic epithelia by an interaction with basolateral K + channels when forskolin was used as the stimulus. (aspetjournals.org)
  • Drug transport requires ATP hydrolysis while, in contrast, ATP binding is sufficient to enable activation of the chloride channel. (cfgenetherapy.org.uk)
  • Selamectin works by replacing glutamate which normally interacts with receptors that open chloride channels at muscle synapses found in parasites. (bionity.com)
  • Unlike glutamate, selamectin activates the chloride current without desensitization, thereby producing prolonged hyperpolarization and impaired muscle contraction. (bionity.com)
  • Arreola, J. 2004-01-01 00:00:00 The effects of external anions (SCN−, NO 3 − , I−, Br−, F−, glutamate, and aspartate) on gating of Ca2+-dependent Cl− channels from rat parotid acinar cells were studied using the whole-cell configuration of the patch-clamp technique. (deepdyve.com)
  • Conclusions: Avermectins are believed to exert their toxicity to invertebrates through interaction with glutamate-gated and GABA-gated chloride channels. (stir.ac.uk)
  • Another pore residue, glutamate 127 (E127), plays an even more critical role in controlling channel conductance. (rupress.org)
  • Primary cultures of rat cerebellar granule neurons are used as an in vitro model because our recent study validated this system for examining the binding profiles of insecticides and their effects on the GABA-gated chloride channel ( Huang and Casida, 1996 ). (aspetjournals.org)
  • 1998), Chloride channel and chloride conductance regul. (xenbase.org)
  • No confirmation for a causal role of volume-regulated chloride channels in ischemic preconditioning in rabbits. (ahajournals.org)
  • Volume-regulated chloride channels associated with the human multidrug-resistance P-glycoprotein. (cfgenetherapy.org.uk)
  • We report here that expression of P-glycoprotein generates volume-regulated, ATP-dependent, chloride-selective channels, with properties similar to channels characterized previously in epithelial cells. (cfgenetherapy.org.uk)
  • Chloride intracellular channel (CLIC) family members were the most abundant chloride channel transcripts, and CLIC1 showed the highest level of expression. (nottingham.ac.uk)
  • XE991 had effects similar to those of 293B on epithelial chloride transport, for which the target is known to be KCNQ1/KCNE3 multimers. (aspetjournals.org)
  • cell membrane glycoproteins selective for chloride ions . (biology-online.org)
  • The selective K(Ca)1.1 blocker paxilline (1 microM) inhibited I(ClCa) by approximately 90%, whereas penitrem A (1 microM) and iberiotoxin (100 and 300 nM) reduced the amplitude of I(ClCa) by approximately 20%, as well as slowing channel deactivation. (sigmaaldrich.com)
  • The generation of action potentials in excitable cells requires selective ion channels that open and close upon changes in membrane potential. (rupress.org)
  • YFP-based probes have been successfully used for quantitative analysis of Cl − transport in different cells and for high-throughput screening of modulators of Cl − -selective channels. (frontiersin.org)
  • When cells swell in hypo-osmotic solutions, chloride-selective ion channels (\(Cl_{swell}\)) activate to reduce intracellular osmolality and prevent catastrophic cell rupture. (harvard.edu)
  • The unique feature of the ClC family is that it contains chloride selective channels and secondary active chloride/proton antiporters. (uzh.ch)
  • For many years, voltage-dependent anion channels were thought to be of no relevance for cell excitability and considered mere "background" or "leakage" channels involved in housekeeping functions. (rupress.org)
  • Experiments that replace wild-type (WT) lysine with neutral or negatively charged residues or that modify the K519C mutant with various methane thiosulfonate (MTS) reagents show that the conductance of the channel decreases when the charge at position 519 is made more negative. (rupress.org)
  • This negatively charged residue, based on the structures of the homologous bacterial ClC channels, lies 4-5 Å from K519. (rupress.org)
  • These channels play important roles in the regulation of chloride homeostasis and cell volume under pathophysiological conditions [ 9 ]. (alliedacademies.org)
  • Chloride channels are a superfamily of poorly understood ion channels specific for chloride. (wikipedia.org)
  • Chloride channels are a superfamily of poorly understood ion channels consisting of approximately 13 members. (bionity.com)
  • Ca 2+ -activated Cl channels were recently discovered to be encoded by members of the anoctamin (Ano, also called Tmem16) superfamily, but the mechanisms of Ano1 gating by Ca 2+ remain enigmatic. (ahajournals.org)
  • This study attempts to resolve these seemingly contradictory results by examining the binding properties of AVM B 1a and its effects on the GABA-gated chloride channel with primary cultures of rat cerebellar granule neurons as a model system. (aspetjournals.org)
  • This study characterizes [3H]EBOB binding and the action of insecticides on the GABA-gated chloride channel of cerebellar granule neurons in primary culture. (aspetjournals.org)
  • The researchers were already able to detect slight kidney damage, but they hope more effects will be discovered: 'At the moment, we assume that a constitutively open chloride channel could also impact other organs,' says group leader Thomas Jentsch. (news-medical.net)
  • At the moment, we assume that a constitutively open chloride channel could also impact other organs," says group leader Thomas Jentsch. (innovations-report.com)
  • CLC Cl(-) channels have roles in the control of electrical excitability, extra- and intracellular ion homeostasis, and transepithelial transport, whereas anion/proton exchangers influence vesicular ion composition and impinge on endocytosis and lysosomal function. (mdc-berlin.de)
  • In this review we discuss the regulation of the different types of Cl− channels found in secretory epithelia. (deepdyve.com)
  • In this report, we examine the effect of XE991 on K + channels in chloride secretory epithelia from the intestine and the airways of mice. (aspetjournals.org)
  • Our objective was to examine if the differences seen with 293B also applied to XE991 and, if so, whether this could be correlated with differences in the type of K + channels present in the two epithelia. (aspetjournals.org)
  • ClC-2 chloride channel is present in the brain and some transporting epithelia where its function is poorly understood. (semanticscholar.org)
  • both channels respond to histamine as well as to GABA. (biologists.org)
  • GABA-A receptor agonists (e.g. lorazepam) may also be considered chloride channel openers Chloride channel blocker Atif M, Estrada-Mondragon A, Nguyen B, Lynch JW, Keramidas A (October 2017). (wikipedia.org)
  • Thus, AVM B 1a binds to two different sites in the GABA-gated chloride channel with dual effects, i.e., activating the channel on binding to the high-affinity site and blocking it on further binding to the low-affinity site. (aspetjournals.org)
  • Robertson, 1989 ), primary cultures of neuronal cells ( Schönrock and Bormann, 1993 ) and neuronal GABA receptor channels expressed in Xenopus oocytes ( Sigel and Baur, 1987 ). (aspetjournals.org)
  • The present study attempts to resolve these seemingly contradictory results by investigating in a new way the binding properties of AVM B 1a and its interactions with the GABA A receptor/chloride channel function. (aspetjournals.org)
  • 4] Each binding site binds different chloride anions simultaneously. (wikipedia.org)
  • CLC-Nt1 may correspond to the inner membrane anion channel ('IMAC') described previously in animal and plant mitochondria. (biochemj.org)
  • One of the earliest studies of anion channel activity was reported in 1979 by White and Miller [ 1 ]. (intechopen.com)
  • This problem has fostered attempts by investigators both to immortalize epithelial cell lines and to search for other cells which may serve as a model to study chloride conductances. (springer.com)
  • The uninhibited single channel displays three "substates" of conductances 20, 10, and 0 pS. (pnas.org)
  • and are perfectly suited to generate large resting chloride conductances while minimally interfering with the upstroke of the action potential. (rupress.org)
  • The objective was to identify regions of Ano1 involved in channel gating by Ca 2+ . (ahajournals.org)