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)

The symptoms of myotonia congenita can vary in severity and may include:

* Muscle stiffness and rigidity, especially in the legs, arms, and neck
* Difficulty relaxing muscles after contraction, leading to prolonged muscle tensing
* Muscle cramps and spasms
* Weakness and fatigue of the muscles
* Delayed or absent deep tendon reflexes
* Abnormal posture or gait
* Difficulty with speech and swallowing in severe cases

Myotonia congenita can be diagnosed through a combination of clinical evaluation, electromyography (EMG), and genetic testing. Treatment for the condition typically involves physical therapy, massage, and relaxation techniques to help manage muscle stiffness and improve mobility. In severe cases, medications such as sodium channel blockers or chloride channel activators may be prescribed to help regulate muscle contraction and relaxation.

Myotonia congenita is a rare condition, and its prevalence is not well established. However, it is estimated to affect approximately 1 in 100,000 to 1 in 200,000 individuals worldwide. The condition can be inherited in an autosomal dominant manner, meaning that a single copy of the mutated gene is enough to cause the condition. However, some cases may be sporadic, meaning they are not inherited from either parent.

Overall, myotonia congenita is a rare and complex genetic disorder that affects the muscles and can significantly impact an individual's quality of life. With proper diagnosis and management, individuals with myotonia congenita can lead fulfilling lives despite the challenges posed by the condition.

There are two main types of myotonia:

1. Thomsen's disease: This is an inherited form of myotonia that affects the muscles of the face, neck, and limbs. It is caused by mutations in the CLCN1 gene and can be severe, causing difficulty with speaking, swallowing, and breathing.
2. Becker's muscular dystrophy: This is a form of muscular dystrophy that affects both the skeletal and cardiac muscles. It is caused by mutations in the DMPK gene and can cause myotonia, muscle weakness, and heart problems.

The symptoms of myotonia can vary depending on the severity of the condition and may include:

* Muscle stiffness and rigidity
* Spasms or twitches
* Difficulty with movement and mobility
* Fatigue and weakness
* Cramps
* Muscle wasting

Myotonia can be diagnosed through a combination of physical examination, medical history, and diagnostic tests such as electromyography (EMG) and muscle biopsy. There is no cure for myotonia, but treatment options may include:

* Physical therapy to improve movement and mobility
* Medications to relax muscles and reduce spasms
* Lifestyle modifications such as avoiding triggers and taking regular breaks to rest
* Surgery in severe cases to release or lengthen affected muscles.

It is important to note that myotonia can be a symptom of other underlying conditions, so proper diagnosis and management by a healthcare professional is essential to determine the best course of treatment.

Symptoms of cystic fibrosis can vary from person to person, but may include:

* Persistent coughing and wheezing
* Thick, sticky mucus that clogs airways and can lead to respiratory infections
* Difficulty gaining weight or growing at the expected rate
* Intestinal blockages or digestive problems
* Fatty stools
* Nausea and vomiting
* Diarrhea
* Rectal prolapse
* Increased risk of liver disease and respiratory failure

Cystic fibrosis is usually diagnosed in infancy, and treatment typically includes a combination of medications, respiratory therapy, and other supportive care. Management of the disease focuses on controlling symptoms, preventing complications, and improving quality of life. With proper treatment and care, many people with cystic fibrosis can lead long, fulfilling lives.

In summary, cystic fibrosis is a genetic disorder that affects the respiratory, digestive, and reproductive systems, causing thick and sticky mucus to build up in these organs, leading to serious health problems. It can be diagnosed in infancy and managed with a combination of medications, respiratory therapy, and other supportive care.

The main symptoms of Bartter Syndrome are:

* Low potassium levels (hypokalemia)
* High aldosterone levels (hyperaldosteronism)
* Normal blood pressure
* Increased urine production (polyuria)
* Dehydration
* Fatigue

Bartter Syndrome can be diagnosed with a combination of clinical evaluation, laboratory tests, and genetic analysis. Treatment for the condition typically involves potassium supplements, dietary restrictions, and medications to control blood pressure and electrolyte levels. In severe cases, dialysis may be required.

The prognosis for Bartter Syndrome is generally good if the condition is properly managed. However, in some cases, the syndrome can progress to more severe forms of kidney disease, such as end-stage renal disease. With proper treatment and management, many individuals with Bartter Syndrome are able to lead normal lives and avoid complications.

Symptoms of nephrocalcinosis may include nausea, vomiting, abdominal pain, frequent urination, and blood in the urine. Diagnosis is typically made through imaging tests such as X-rays, CT scans, or ultrasound, and blood tests to determine calcium levels and kidney function.

Treatment for nephrocalcinosis depends on the underlying cause of the condition and may include medications to lower calcium levels, dietary changes to reduce calcium intake, and in severe cases, dialysis or kidney transplantation may be necessary. It is important to seek medical attention if symptoms persist or worsen over time, as early detection and treatment can help prevent long-term damage to the kidneys.

There are several types of channelopathies, including:

1. Long QT syndrome: This is a condition that affects the ion channels in the heart, leading to abnormal heart rhythms and increased risk of sudden death.
2. Short QT syndrome: This is a rare condition that has the opposite effect of long QT syndrome, causing the heart to beat too quickly.
3. Catecholaminergic polymorphic ventricular tachycardia (CPVT): This is a rare disorder that affects the ion channels in the heart, leading to abnormal heart rhythms and increased risk of sudden death.
4. Brugada syndrome: This is a condition that affects the ion channels in the heart, leading to abnormal heart rhythms and increased risk of sudden death.
5. Wolff-Parkinson-White (WPW) syndrome: This is a condition that affects the ion channels in the heart, leading to abnormal heart rhythms and increased risk of sudden death.
6. Neuromuscular disorders: These are disorders that affect the nerve-muscle junction, leading to muscle weakness and wasting. Examples include muscular dystrophy and myasthenia gravis.
7. Dystrophinopathies: These are a group of disorders that affect the structure of muscle cells, leading to muscle weakness and wasting. Examples include Duchenne muscular dystrophy and Becker muscular dystrophy.
8. Myotonia: This is a condition that affects the muscles, causing them to become stiff and rigid.
9. Hyperkalemic periodic paralysis: This is a rare condition that causes muscle weakness and paralysis due to abnormal potassium levels in the body.
10. Hypokalemic periodic paralysis: This is a rare condition that causes muscle weakness and paralysis due to low potassium levels in the body.
11. Thyrotoxic periodic paralysis: This is a rare condition that causes muscle weakness and paralysis due to an overactive thyroid gland.
12. Hyperthyroidism: This is a condition where the thyroid gland becomes overactive, leading to increased heart rate, weight loss, and muscle weakness.
13. Hypothyroidism: This is a condition where the thyroid gland becomes underactive, leading to fatigue, weight gain, and muscle weakness.
14. Pituitary tumors: These are tumors that affect the pituitary gland, which regulates hormone production in the body.
15. Adrenal tumors: These are tumors that affect the adrenal glands, which produce hormones such as cortisol and aldosterone.
16. Carcinoid syndrome: This is a condition where cancer cells in the digestive system produce hormones that can cause muscle weakness and wasting.
17. Multiple endocrine neoplasia (MEN): This is a genetic disorder that affects the endocrine system and can cause tumors to grow in the thyroid, adrenal, and parathyroid glands.

These are just some of the many potential causes of muscle weakness. It's important to see a healthcare professional for an accurate diagnosis and appropriate treatment.

There are several types of kidney calculi, including:

1. Calcium oxalate calculi: These are the most common type of calculus and are often associated with conditions such as hyperparathyroidism or excessive intake of calcium supplements.
2. Uric acid calculi: These are more common in people with gout or a diet high in meat and sugar.
3. Cystine calculi: These are rare and usually associated with a genetic disorder called cystinuria.
4. Struvite calculi: These are often seen in women with urinary tract infections (UTIs).

Symptoms of kidney calculi may include:

1. Flank pain (pain in the side or back)
2. Pain while urinating
3. Blood in the urine
4. Cloudy or strong-smelling urine
5. Fever and chills
6. Nausea and vomiting

Kidney calculi are diagnosed through a combination of physical examination, medical history, and diagnostic tests such as X-rays, CT scans, or ultrasound. Treatment options for kidney calculi depend on the size and location of the calculus, as well as the severity of any underlying conditions. Small calculi may be treated with conservative measures such as fluid intake and medication to help flush out the crystals, while larger calculi may require surgical intervention to remove them.

Preventive measures for kidney calculi include staying hydrated to help flush out excess minerals in the urine, maintaining a balanced diet low in oxalate and animal protein, and avoiding certain medications that can increase the risk of calculus formation. Early detection and treatment of underlying conditions such as hyperparathyroidism or gout can also help prevent the development of kidney calculi.

Overall, kidney calculi are a common condition that can be managed with proper diagnosis and treatment. However, they can cause significant discomfort and potentially lead to complications if left untreated, so it is important to seek medical attention if symptoms persist or worsen over time.

Examples of inborn errors of renal tubular transport include:

1. Cystinuria: This is a disorder that affects the reabsorption of cystine, an amino acid, in the renal tubules. It can lead to the formation of cystine stones in the kidneys.
2. Lowe syndrome: This is a rare genetic disorder that affects the transport of sodium and potassium ions across the renal tubules. It can cause a range of symptoms, including delayed development, intellectual disability, and seizures.
3. Glycine encephalopathy: This is a rare genetic disorder that affects the transport of glycine, an amino acid, across the renal tubules. It can cause a range of symptoms, including muscle weakness, developmental delays, and seizures.
4. Hartnup disease: This is a rare genetic disorder that affects the transport of tryptophan, an amino acid, across the renal tubules. It can cause a range of symptoms, including diarrhea, weight loss, and skin lesions.
5. Maple syrup urine disease: This is a rare genetic disorder that affects the transport of branched-chain amino acids (leucine, isoleucine, and valine) across the renal tubules. It can cause a range of symptoms, including seizures, developmental delays, and kidney damage.

Inborn errors of renal tubular transport can be diagnosed through a combination of clinical evaluation, laboratory tests, and genetic analysis. Treatment depends on the specific disorder and may include dietary modifications, medications, and dialysis. Early detection and treatment can help manage symptoms and prevent complications.

The word "osteopetrosis" comes from the Greek words "osteon," meaning bone, and "petros," meaning rock or stone. This name reflects the dense and hard nature of the bones affected by the disorder.

Osteopetrosis can be caused by mutations in several genes that are involved in bone development and growth. The condition is usually inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to cause the disorder. However, some cases may be caused by spontaneous mutations or other factors.

Symptoms of osteopetrosis can vary depending on the severity of the disorder and the specific affected bones. Common symptoms include bone pain, limited mobility, and an increased risk of fractures. Other symptoms may include fatigue, fever, and difficulty swallowing or breathing.

Treatment for osteopetrosis usually involves a combination of medications and surgery. Medications such as bisphosphonates and denintuzumab mafodotin can help reduce bone pain and the risk of fractures, while surgery may be necessary to correct deformities or repair broken bones. In some cases, bone marrow transplantation may be recommended to replace damaged bone marrow with healthy cells.

Overall, osteopetrosis is a rare and debilitating disorder that can have a significant impact on quality of life. Early diagnosis and appropriate treatment are important for managing symptoms and preventing complications.

There are two main types of myotonic dystrophy:

1. Type 1 (also known as DM1): This is the most common form of the disorder and affects about 90% of all cases. It is caused by a mutation in the DMPK gene on chromosome 19.
2. Type 2 (also known as DM2): This form of the disorder is less common and affects about 10% of all cases. It is caused by a mutation in the CNBP gene on chromosome 3.

Symptoms of myotonic dystrophy typically appear in adults between the ages of 20 and 40, but can sometimes be present at birth. They may include:

* Muscle stiffness and rigidity
* Weakness of the face, neck, and limbs
* Difficulty swallowing (dysphagia)
* Difficulty speaking or slurred speech (dysarthria)
* Eye problems, such as cataracts or muscle imbalance in the eyelids
* Cramps and muscle spasms
* Fatigue and weakness
* Slowed muscle relaxation after contraction (myotonia)

Myotonic dystrophy is diagnosed through a combination of physical examination, medical history, and genetic testing. There is currently no cure for the disorder, but various treatments can help manage symptoms and slow its progression. These may include:

* Physical therapy to improve muscle strength and function
* Medications to relax muscles and reduce spasms
* Speech therapy to improve communication and swallowing difficulties
* Occupational therapy to assist with daily activities and independence
* Orthotics and assistive devices to help with mobility and other challenges

It is important for individuals with myotonic dystrophy to work closely with their healthcare providers to manage their symptoms and maintain a good quality of life. With appropriate treatment and support, many people with the disorder are able to lead active and fulfilling lives.

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", ...
... 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 ... v t e (CS1: long volume value, Drugs, Ion channel blockers, Chloride channel blockers, All stub articles, Pharmacology stubs). ... 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'- ...
... chloride channel accessory (CLCA), bestrophin (BEST), and calcium-dependent chloride channel anoctamin (ANO or TMEM16) channels ... The Calcium-Dependent Chloride Channel (Ca-ClC) proteins (or calcium-activated chloride channels (CaCCs), are heterogeneous ... "1.A.17 The Calcium-Dependent Chloride Channel (Ca-ClC) Family". TCDB. Retrieved 16 April 2016. "Calcium activated chloride ... possibly as Ca2+ channels or Ca2+ channel subunits (see also family TC# 1.A.82). Mice lacking both channels lack hair cell ...
It can flow through chloride channels (including the GABAA receptor) and is transported by KCC2 and NKCC2 transporters. ... Some chloride-containing minerals include halite (sodium chloride NaCl), sylvite (potassium chloride KCl), bischofite (MgCl2∙ ... Salts such as calcium chloride, magnesium chloride, potassium chloride have varied uses ranging from medical treatments to ... such as silver chloride, lead(II) chloride, and mercury(I) chloride, they are only slightly soluble in water. In aqueous ...
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- ...
Hartzell, Criss; Putzier, Ilva; Arreola, Jorge (2005-03-17). "Calcium -activated chloride channels". Annual Review of ... In selective ion channels, the favoured ionic species passes through the channel almost at the rate of free diffusion, despite ... blockade that has been observed in biological chloride ( Cl − {\displaystyle {\ce {Cl-}}} )-selective channels. ICB and ECB ... "Calcium channel characteristics conferred on the sodium channel by single mutations". Nature. 356 (6368): 441-443. Bibcode: ...
Voltage-gated potassium channels (Kv), Sodium channels (Nav), Calcium channels (Cav) and Chloride channels (ClC) Intracellular ... Sodium channels Voltage-gated sodium channels (NaVs) Epithelial sodium channels (ENaCs) Calcium channels (CaVs) Proton channels ... These are classified by the channel on which they act: Calcium channel openers, such as Bay K8644 Chloride channel openers, ... however chloride is the most abundant anion, and hence they are known as chloride channels. Potassium channels Voltage-gated ...
Chloride channel Kb, also known as CLCNKB, is a protein which in humans is encoded by the CLCNKB gene. Chloride channel Kb ( ... is a member of the CLC family of voltage-gated chloride channels, which comprises at least 9 mammalian chloride channels. Each ... Chloride channel BSND, barttin, accessory subunit beta for this channel GRCh38: Ensembl release 89: ENSG00000184908 - Ensembl, ... "Entrez Gene: CLCNKB chloride channel Kb". Saito-Ohara F, Uchida S, Takeuchi Y, Sasaki S, Hayashi A, Marumo F, Ikeuchi T ( ...
Chloride channel 7 alpha subunit also known as H+/Cl− exchange transporter 7 is a protein that in humans is encoded by the ... "Entrez Gene: CLCN7 chloride channel 7". Meadows NA, Sharma SM, Faulkner GJ, Ostrowski MC, Hume DA, Cassady AI (2007). "The ... 2004). "Chloride channel 7 (ClCN7) gene mutations and autosomal dominant osteopetrosis, type II". J. Bone Miner. Res. 18 (8): ... Brandt S, Jentsch TJ (1996). "ClC-6 and ClC-7 are two novel broadly expressed members of the CLC chloride channel family". FEBS ...
Chloride channel 4 has an evolutionary conserved CpG island and is conserved in both mouse and hamster. This gene is mapped in ... "Entrez Gene: CLCN4 chloride channel 4". Veeramah KR, Johnstone L, Karafet TM, Wolf D, Sprissler R, Salogiannis J, Barth-Maron A ... Lamb FS, Clayton GH, Liu BX, Smith RL, Barna TJ, Schutte BC (1999). "Expression of CLCN voltage-gated chloride channel genes in ... The CLCN family of voltage-dependent chloride channel genes comprises nine members (CLCN1-7, Ka and Kb) which demonstrate quite ...
... channel blockers Chloride (Cl−) channel blockers Potassium (K+) channel blockers Sodium (Na+) channel blockers The following ... Various ion channels have varying mechanisms of function. They include: voltage-gated ion channels Ion channels that are ... Channel blockers are antagonists for the respective ion channels. Many channels have binding spots for regulatory elements ... Ion channel Channel opener "Medical Definition of Ion channel". MedicineNet. Retrieved 2017-03-20. Kocahan S, Doğan Z (February ...
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 channel 6 and 7 belong to a subbranch of this family. Chloride channel 6 has four different alternatively spliced ... This gene is in close vicinity to two other kidney-specific chloride channel genes, CLCNKA and CLCNKB. Chloride channel GRCh38 ... "Entrez Gene: CLCN6 chloride channel 6". Nakajima D, Okazaki N, Yamakawa H, et al. (2003). "Construction of expression-ready ... Brandt S, Jentsch TJ (Feb 1996). "ClC-6 and ClC-7 are two novel broadly expressed members of the CLC chloride channel family". ...
... chloride channel 3". Gentzsch M, Cui L, Mengos A, Chang XB, Chen JH, Riordan JR (Feb 2003). "The PDZ-binding chloride ... Gentzsch M, Cui L, Mengos A, Chang XB, Chen JH, Riordan JR (2003). "The PDZ-binding chloride channel ClC-3B localizes to the ... Lamb FS, Clayton GH, Liu BX, Smith RL, Barna TJ, Schutte BC (1999). "Expression of CLCN voltage-gated chloride channel genes in ... Lamb FS, Graeff RW, Clayton GH, Smith RL, Schutte BC, McCray PB (2001). "Ontogeny of CLCN3 chloride channel gene expression in ...
... 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 ...
"LOC100419056 chloride channel, voltage-sensitive 3 pseudogene". NCBI. Retrieved 13 May 2013. "TTC39B, a comprehensive ... TTC39B is surrounded by LOC100419056, a chloride channel, voltage-sensitive 3 pseudogene. TTC39B is expected to have a ... TPR motifs that are arranged one in front of another create a right-handed helical structure with an amphipathic channel which ...
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 ...
It inhibits γ-aminobutyric acid (GABA)-gated chloride channels (GABAA receptors) resulting in uncontrolled hyperactivity of the ... Antagonists and Modulators of Chloride Channels". In Mehlhorn H (ed.). Encyclopedia of Parasitology (3rd ed.). Berlin: Springer ...
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. ...
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 ...
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. ...
Hille, Bertil (2001). "Chapter 5: Potassium Channels and Chloride Channels". Ion channels of excitable membranes. Sunderland, ... Proteopedia channel Potassium channel in 3D Potassium+Channels at the US National Library of Medicine Medical Subject Headings ... Calcium channel - Ion channel complex through which calcium ions pass Inward-rectifier potassium ion channel Potassium in ... see potassium channel blocker and potassium channel opener. Potassium channels have a tetrameric structure in which four ...
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 ...
Gentzsch M, Cui L, Mengos A, Chang XB, Chen JH, Riordan JR (February 2003). "The PDZ-binding chloride channel ClC-3B localizes ... Cormet-Boyaka E, Di A, Chang SY, Naren AP, Tousson A, Nelson DJ, Kirk KL (September 2002). "CFTR chloride channels are ... Mutations of the CFTR gene affecting chloride ion channel function lead to dysregulation of epithelial lining fluid (mucus) ... Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and chloride channel in vertebrates that is ...
Altered splicing of the muscle-specific chloride channel 1 (ClC-1) has been shown to cause the myotonic phenotype of DM1 and is ... Functional loss of the chloride channel causes myotonia. In DM1, there can be increased central nuclei, angular fibers, fiber ... One example in DM1 involves the chloride channel ClC-1. Mutated DMPK RNA binds to MBNL1, causing ClC-1 pre-mRNA to be spliced ... Wheeler TM, Lueck JD, Swanson MS, Dirksen RT, Thornton CA (December 2007). "Correction of ClC-1 splicing eliminates chloride ...
"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 ...
Fan L, Yu W, Zhu X (April 2003). "Interaction of Sedlin with chloride intracellular channel proteins". FEBS Letters. 540 (1-3 ... Fan L, Yu W, Zhu X (April 2003). "Interaction of Sedlin with chloride intracellular channel proteins". FEBS Letters. 540 (1-3 ...
The type A GABA receptors are pentameric chloride channels assembled from among many genetic variants of GABA(A) subunits. This ... Ion channels, All stub articles, Membrane protein stubs). ...
Reilly, Michael; The Discovery Channel. "World's oldest known DNA discovered". Retrieved 3 September 2010. Park, J. S.; ... potassium chloride) to reduce osmotic stress. Potassium levels are not at equilibrium with the environment, so H. salinarum ...
For example, muscle contraction depends upon the movement of calcium, sodium and potassium through ion channels in the cell ... The most important ions are sodium, potassium, calcium, magnesium, chloride, phosphate and the organic ion bicarbonate. The ... Electrolytes enter and leave cells through proteins in the cell membrane called ion channels. ...
... causing an increase in opening frequency of the chloride ion channel which results in an increased influx of chloride ions into ...
... polycystin cation channels, glutamate-gated ion channels, calcium-dependent chloride channels, monovalent cation:proton ... Chloride channels are present in all types of neurons. With the chief responsibility of controlling excitability, chloride ... this type of channel differs in function between cell types. Ca2+ channels produce action potentials similarly to Na+ channels ... Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in 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 have been hypothesized to give rise to an inward current that may play an important role in the ... L-type calcium channels are known to increase the frequency of action potentials in some neurons, which might be the reason ...
... which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as ... Ion channels, All stub articles, Membrane protein stubs). ...
Calcium release from IP3 sensitive calcium stores activates calcium dependent chloride channels. These chloride channels ... The specific mechanism for the contraction of smooth muscle in the GI tract depends upon IP3R calcium release channels in the ...
When the neuron is depolarizing, the CNG ion channel is open allowing sodium and calcium to rush into the cell. The influx of ... and an efflux of chloride ions. This influx of positive ions and efflux of negative ions causes the neuron to depolarize, ... CaM will then bind to the CNG channel and close it, stopping the sodium and calcium influx. CaMKII will be activated by the ... Touhara, Kazushige (2009). "Insect Olfactory Receptor Complex Functions as a Ligand-gated Ionotropic Channel". Annals of the ...
doi:10.1061/(ASCE)0733-9372(2000)126:10(974). "'Obnoxious Odor' A Lemon Makes". The Auto Channel. Truong, Alice (20 November ... polyvinyl chloride, or PVC), and heavy metals that off-gas from various parts such as the steering wheel, dashboard, armrests ...
After running a second test, however, the coroner confirmed that someone had given MacKenzie potassium chloride to induce a ... making it the third most-watched program for the channel behind Game of Thrones and Blue Bloods. "The Little Guy" has generally ...
It is divided into the northern (98 km²) and the southern (149 km²) sub-basins, which are linked by a narrow channel. The ... Under this project, the lake is expected to produce 20,000 tonnes of lithium salt, 5,000 tonnes of lithium chloride, 500 tonnes ... ISBN 0-7923-4098-1. Donald E. Garrett Handbook of lithium and natural calcium chloride: their deposits, processing, Academic ...
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. Certain ... The channel conductance is not higher in the presence of benzodiazepine and GABA than the conductance with the presence of only ... But if the γ2 is expressed with α1 and β2 the sensitivity is low and channel conductance is high. γ2 subunit has to be present ...
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 and a (Dipyridin-2-ylmethyl)amine-DerivedPalladium(II) Chloride Complex as Highly Efficient Catalysts for the ... and of aryl chlorides, but in very low yields. The dendrimeric catalysts could usually be recovered by simple precipitation and ...
... and large conductance calcium-activated potassium channel (BKCa) are the two primary channels for potassium secretion. WNK1 ... The predominant role of WNK1 is the regulation of cation-Cl− cotransporters (CCCs) such as the sodium chloride cotransporter ( ... WNK1 regulates potassium channels found in the cortical collecting duct (CCD) and connecting tubule (CNT). Renal outer medullar ... GABA activates the GABAA receptor which is a Cl− ion channel. Cl− ions will enter the neuron causing hyperpolarization and ...
Zhang W, Na T, Peng JB (2008). "WNK3 positively regulates epithelial calcium channels TRPV5 and TRPV6 via a kinase-dependent ... Ko B, Hoover RS (2009). "Molecular physiology of the thiazide-sensitive sodium-chloride cotransporter". Curr. Opin. Nephrol. ... 2010). "Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no ...
This force allows for the systems to be used as receptors and channels in supramolecular chemistry for applications in the ... Cores as Highly Efficient Catalysts for the Coupling of Aryl Chlorides". Organometallics. 27 (22): 5911. doi:10.1021/om800711g ... Kumpf, R.; Dougherty, D. (1993). "A mechanism for ion selectivity in potassium channels: computational studies of cation-pi ... medical (synthetic membranes, ion channels) and environmental fields (e.g. sensing, removal of ions from water). The first X- ...
In 1966, the Soviet team repeated the experiment using a chemical study of volatile chloride products. They identified a ... represents an observed exit channel. The table below provides cross-sections and excitation energies for hot fusion reactions ... represents an observed exit channel. Sonzogni, Alejandro. "Interactive Chart of Nuclides". National Nuclear Data Center: ... volatile chloride with eka-hafnium properties that decayed fast through spontaneous fission. This gave strong evidence for the ...
These cells have sodium-chloride symporter at distal convoluted tubule, epithelial sodium channels, and chloride-bicarbonate ... Thiazide (blockade of sodium-chloride symporter), amiloride (blockade of epithelial sodium channels) and carbonic anhydrase ... The difference in voltage in both sides are set up by potassium recycling through renal outer medullary potassium channel. By ... chloride and potassium reabsorption. This is achieved by competing for the Cl− binding site. Loop diuretics also inhibits NKCC2 ...
... chloride channel - chlorophyll - chloroplast - chloroplast membrane - cholecystokinin receptor - cholesterine - cholinergic ... Ion channel - ion channel gating - Ionic bond - ionization potential - iron-sulfur protein - isoenzyme - isoleucine - Isomer - ... calcium channel - calcium signaling - calcium-binding protein - calmodulin - calmodulin-binding protein - Calvin cycle - CAM ... potassium channel - potential energy - pregnancy proteins - primary nutritional groups - primary structure - primer - prion - ...
The streams found in Rouge Park have shown an overall increase in levels of chloride. Noise created by the highway can also ... Many decades of urban development have led to increased erosion and channel instability. Erosion can cause sediment loading in ...
Some ripples and a small channel are also visible. Glaciers formed much of the observable surface in large areas of Mars. Much ... Results published in the journal Science after the Phoenix mission ended reported that chloride, bicarbonate, magnesium, sodium ...
The molds are controlled through a split via a channel system of gates and runners. EPS is colloquially called "styrofoam" in ... The process involved irradiation of polystyrene with iron chloride and acetone under white light and oxygen for 20 hours. The ... "Foul Play Considered in Channel Tunnel Fire Inquiry". The Irish Times. 28 November 1996. Retrieved 14 January 2018. This ... for example at the Düsseldorf International Airport and in the Channel Tunnel (where polystyrene was inside a railway carriage ...
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 ...
The scientists claim that their studies using a single channel fast Fourier transform (FFT) and multiple channel system ... The arrayed electrode was also demonstrated to perform well compared to silver/silver chloride electrodes. The device consisted ... Bin G, Gao X, Yan Z, Hong B, Gao S (August 2009). "An online multi-channel SSVEP-based brain-computer interface using a ... The tutorial, which stirred the minds of many budding DIY BCI enthusiasts, demonstrated how to create a single channel at-home ...
2012). "The Calcium-activated Chloride Channel Anoctamin 1 acts as a Heat Sensor in Nociceptive Neurons". Nature Neuroscience. ... The Calcium-activated Chloride Channel Anoctamin 1 acts as a Heat Sensor in Nociceptive Neurons. Nature Neuroscience (2012) ... Proc Natl Acad Sci USA 1996: Oh U et al., Capsaicin Activates a Non-selective Cation Channel in Cultured Neonatal Rat Dorsal- ... Proc Natl Acad Sci USA (2002) 2002: Cho H et al., Mechano-sensitive Ion Channels in Cultured Sensory Neurons of Neonatal Rats. ...
Apple responded by declaring that they did not call for the channels to be removed, but instead asked him to delete personal ... speed up the phase-out of toxic chemicals such as polyvinyl chloride (PVC) and brominated flame retardants (BFRs), and adopt a ... "Apple claims it has not requested blocking of Telegram channels on Belarus". TASS. Retrieved 2019-09-09. James Vincent (August ... bypassing the App Store and the official release channels that do not grant required permissions for f.lux to work. A day later ...
NETs have conductances similar to those of ligand-gated ion channels. The expression of NET results in a leak-channel activity ... NET functions by coupling the influx of sodium and chloride (Na+/Cl−) with the transport of norepinephrine. This occurs at a ... Recently discovered mechanisms of the NET, including the ability to act reversibly and as an ion channel, provide other areas ... NET is a monoamine transporter and is responsible for the sodium-chloride (Na+/Cl−)-dependent reuptake of extracellular ...
Calcium-activated chloride channel A4 (CLCA4) is known as a tumor suppressor which contributes to the progression of a number ... Calcium-Activated Chloride Channel A4 (CLCA4) Plays Inhibitory Roles in Invasion and Migration Through Suppressing Epithelial- ... BACKGROUND: Calcium-activated chloride channel A4 (CLCA4) is known as a tumor suppressor which contributes to the progression ... Chloride Channels, Databases, Genetic, Disease Progression, Kaplan-Meier Estimate, Middle Aged, Phosphatidylinositol 3-Kinases ...
4-(Furan-2-yl)-1,4-dihydropyridine derivatives potentiate the CFTR chloride channel. CATENI, FRANCESCA;ZACCHIGNA, MARINA; ... Studies of Molecular Modeling on DHPs are in progress: our preliminary data show that DHPs lay into a channel near to the ATP ... Studies of Molecular Modeling on DHPs are in progress: our preliminary data show that DHPs lay into a channel near to the ATP ... It has been shown that mutant CFTR is activated by DHPs through a mechanism not involving the modulation of Ca++ channels, but ...
The chloride (Cl-) channel cystic fibrosis transmembrane conductance regulator (CFTR) is defective in cystic fibrosis (CF), and ... Development of Automated Patch Clamp Technique to Investigate CFTR Chloride Channel Function. Journal: Frontiers in ... abnormal channel gating with low open probability, and thermal instability, which leads to inactivation of the channel at ...
Chloride Channel Agonists. Membrane Transport Modulators. Molecular Mechanisms of Pharmacological Action. To Top ... Absolute Change in Sweat Chloride (SwCl) [ Time Frame: From Baseline at Week 4 ]. Sweat samples were collected using an ...
CFTR is the secretory chloride/HCO3− channel; its dysfunction causes acidification of the mucus layer (pH , 6.5) due to ... calcium-activated chloride channel regulator 1), and ZG16 (zymogen granule protein 16), in active UC support the notion that an ... Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus ... Bacteroides fragilis can penetrate the colonic mucus and reside deep within crypt channels, whereas strains with CCF mutations ...
TMEM16A Ca2+-activated chloride channel (CaCC) plays an essential role in vascular homeostasis. In this study we investigated ... Endophilin A2 regulates calcium-activated chloride channel activity via selective autophagy-mediated TMEM16A degradation.. Liu ...
... calcium-activated chloride channel-2; chloride channel accessory 2; chloride channel regulator 2; chloride channel, calcium ... Calcium-activated chloride channel family member 2; Calcium-activated chloride channel protein 3; calcium-activated chloride ... chloride channel regulator; CLCA2; CLCRG2; FLJ97885; hCaCC-3; hCLCA2 ...
Name: chloride channel accessory 2. Synonyms: Clca5. Type: Gene. Species: Mus musculus (mouse) ...
Gene Description: chloride intracellular channel 6. Synonyms: 5730466J16Rik, CLIC1L. Gene Family:. Ion Channel ...
Chloride channel activators (eg, lubiprostone). * Guanylate cyclase C (GC-C) agonists (eg, linaclotide, plecanatide) ...
A Visible-Light-Regulated Chloride Transport Channel Inspired by Rhodopsin. Angewandte Chemie, 133(6), 2928-2933. ... A Visible-Light-Regulated Chloride Transport Channel Inspired by Rhodopsin. Angewandte Chemie - International Edition, 60(6), ... 2021). Construction of A High-Flux Protein Transport Channel Inspired by the Nuclear Pore Complex. Angewandte Chemie - ...
... which provide instructions for making chloride channels. Learn about this gene and related health conditions. ... Some CLC channels regulate the flow of chloride ions across cell membranes, while others transport chloride ions within cells. ... ClC-7 channels help regulate the relative acidity (pH) of osteoclasts. These channels transport two negatively charged chloride ... The CLCN7 gene belongs to the CLC family of genes, which provide instructions for making chloride channels. These channels, ...
AMITIZA (lubiprostone) is a chloride channel activator that acts locally in the small intestine. By increasing intestinal fluid ... Lubiprostone, via activation of apical CIC-2 channels in intestinal epithelial cells, bypasses the antisecretory action of ...
CLCA1 (calcium-activated chloride channel regulator 1) was the most upregulated gene transcript (>100-fold) in all exposed ... Analysis of lung gene expression reveals a role for Cl- channels in diisocyanate induced airway eosinophilia in a mouse model ... Crofelemer, a U.S. Food and Drug Administration-approved Cl- channel inhibitor, reduced MDI exposure induction of airway ... In addition to chemokines and alternatively activated monocytes/macrophages, the data suggest a crucial role for Cl- channels ...
"Chloride channels in the Nuclear membrane" (PDF). Harvard.edu. Arhivirano s originala (PDF), 2. 8. 2010. Pristupljeno 7. 12. ...
Cell volume regulation and swelling-activated chloride channels. Sardini, A., Amey, J.S., Weylandt, K.H., Nobles, M., Valverde ... Cell volume regulation and swelling-activated chloride channels.. Maintenance of a constant volume is essential for normal cell ... a member of the ClC family which has been recently proposed as the chloride channel involved in cell volume regulation.[1]. ... Several proteins have been proposed as candidates for this chloride conductance. The status of the field is reviewed, with ...
No biologic or pharmacologic therapies directed at the primary chloride channel defect currently are available. However, ... and bypassing CFTR-mediated chloride transport and using alternative channels. Clinical Course of Infants with Cystic Fibrosis ... The CF status of all infants was determined by a sweat chloride test after screening with either a single-tier IRT or two-tier ... Sweat chloride concentrations in infants homozygous or heterozygous for DF508 cystic fibrosis. Pediatrics 1996;97:524-8. ...
Each channel has a multimeric structure with several subunits of different types. Chloride channels are no exception; they have ... In the end, the behavior of all individual chloride channels sum up to form a large chloride-mediated hyperpolarizing current ... The reversal potential of chloride is about negative 70 mV. The contribution of chloride channels during resting potential in ... Alterations in the normal state of the chloride channels may increase the membrane permeability and conductance of chloride ...
Differentiation induced polarized expression of collecting duct water channels AQP2 and AQP3 and a physiological response to ... Differentiation resulted in polarized expression of collecting duct water channels AQP2 and AQP3. Also, a physiological ... including the water channel AQP2 and the sodium channel ENaC. ... including the water channel AQP2 and the sodium channel ENaC. ... 0.15 M sodium chloride, 0.1 M Tris-HCl, pH 7.6) with 0.1% (v/v) Triton X-100 and blocked for 30 min using TN with 0.5% (w/v) ...
Cystic fibrosis is a disease caused by defective function of a chloride channel coupled to a blockade of autophagic flux. It ... Here, we report that such chloride anionophores block autophagic flux in spite of the fact that th... ... Author Correction: Squaramide-based synthetic chloride transporters activate TFEB but block autophagic flux ... has been proposed to use synthetic chloride transporters as pharmacological agents to compensate insufficient chloride fluxes. ...
Chloride channels as drug targets. Nat Rev Drug Discov. 2009;8(2):153-171.. View this article via: PubMed CrossRef Google ... using a chloride concentration gradient with high chloride buffer in the basolateral chamber and low chloride buffer in the ... Multi-ion pore behaviour in the CFTR chloride channel. Nature. 1993;366(6450):79-82.. View this article via: PubMed CrossRef ... Dual roles of the sixth transmembrane segment of the CFTR chloride channel in gating and permeation. J Gen Physiol. 2010;136(3 ...
Evolving drugs include lubiprostone, which enhances colonic secretion by activating chloride channels. Surgery is restricted ... Evolving drugs include lubiprostone, which enhances colonic secretion by activating chloride channels. Surgery is restricted ... Evolving drugs include lubiprostone, which enhances colonic secretion by activating chloride channels. Surgery is restricted ...
... exaggerated alteration of ozone-targeted chloride channels [16,17]. The activation of chloride channels modulation should ... A possibility, though yet speculative thus far, is that ozone may target chloride channels in human lung epithelial cells and ... Selective inhibition of the K+ efflux sensitive NLRP3 pathway by Cl− channel modulation. Chem. Sci. 2020, 11, 11720-11728. [ ... Modulation of Chloride Currents in Human Lung Epithelial Cells Exposed to Exogenous Oxidative Stress. J. Cell. Physiol. 2017, ...
Moxidectin acts by interfering with chloride channel-medicated neurotransmission in the parasite. This results in paralysis and ...
Chloride dependence of hyperpolarization-activated chloride channel gates.. 515 ( Pt 2):341-353. 1999 ... Hyposmotically activated chloride channels in cultured rabbit non-pigmented ciliary epithelial cells.. 521 Pt 1:57-67. 1999 ... Role of voltage-dependent calcium channels in stimulus-secretion coupling in rabbit carotid body chemoreceptor cells. 562:407- ... GYGD pore motifs in neighbouring potassium channel subunits interact to determine ion selectivity.. 530:21-33. 2001 ...
In Silico Analysis of Novel and Known Mutations in the Human Dimeric Skeletal Muscle Chloride Channel SKÁLOVÁ Daniela ZÍDKOVÁ ...
  • Negatively charged chloride can cross biological membranes only with the help of membrane-spanning proteins such as Cl - channels, which allow passive diffusion of Cl - along its electrochemical gradient, or transporter proteins that couple the movement of Cl - to that of other ions and can thereby establish electrochemical gradients. (elifesciences.org)
  • CLCA1 was labeled a chloride channel because it appeared to be moving chloride ions across the cell membrane. (genengnews.com)
  • The ClC-Ka and ClC-Kb channels transport charged atoms of chlorine (chloride ions) out of kidney cells. (medlineplus.gov)
  • The transport of chloride ions is part of the mechanism by which the kidneys reabsorb salt (sodium chloride or NaCl) from the urine back into the bloodstream. (medlineplus.gov)
  • Other mutations allow the channels to reach the cell membrane but prevent them from transporting ions properly. (medlineplus.gov)
  • The channel transports negatively charged particles called chloride ions into and out of cells. (nih.gov)
  • The transport of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus. (nih.gov)
  • The CFTR protein also regulates the function of other channels, such as those that transport positively charged particles called sodium ions across cell membranes. (nih.gov)
  • Mutations in the CFTR gene disrupt the function of the chloride channel, preventing the usual flow of chloride ions and water into and out of cells. (nih.gov)
  • The resulting abnormal channel breaks down shortly after it is made, so it never reaches the cell membrane to transport chloride ions. (nih.gov)
  • All of these changes prevent the channel from functioning properly, which impairs the transport of chloride ions and the movement of water into and out of cells. (nih.gov)
  • Cell membrane glycoproteins that form channels to selectively pass chloride ions. (nih.gov)
  • The chloride (Cl - ) channel cystic fibrosis transmembrane conductance regulator (CFTR) is defective in cystic fibrosis (CF), and mutation of its encoding gene leads to various defects such as retention of the misfolded protein in the endoplasmic reticulum, reduced stability at the plasma membrane, abnormal channel gating with low open probability, and thermal instability, which leads to inactivation of the channel at physiological temperature. (sophion.com)
  • 3. The intracellular chloride channel 4 (CLIC4) activates systemic sclerosis fibroblasts. (nih.gov)
  • Cobiprostone is a locally acting chloride channel activator that works to stimulate and protect the mucosal barrier function. (nursingcenter.com)
  • TMEM16A Ca2+-activated chloride channel ( CaCC ) plays an essential role in vascular homeostasis . (bvsalud.org)
  • For instance, deletion of phenylalanine at position 508 (DF508), the most frequent mutation (occurring in more than 50-70 % of patients), causes both a severe defect of CFTR protein processing (trafficking defect) and a decrease of its channel activity (gating defect). (units.it)
  • It has been shown that mutant CFTR is activated by DHPs through a mechanism not involving the modulation of Ca++ channels, but the direct interaction with the CFTR protein itself. (units.it)
  • Studies of Molecular Modeling on DHPs are in progress: our preliminary data show that DHPs lay into a channel near to the ATP pocket in NBD1 of CFTR (Figure 2): the presence of Potentiators in this site could make more difficult the hydrolysis of ATP, having as a consequence a longer opening time of the CFTR channel. (units.it)
  • Disease-causing mutations in the CFTR gene alter the production, structure, or stability of the chloride channel. (nih.gov)
  • This protein is found primarily in the kidneys, where it attaches (binds) to two specific chloride channels: ClC-Ka (produced from the CLCNKA gene) and ClC-Kb (produced from the CLCNKB gene). (medlineplus.gov)
  • BSND gene mutations impair barttin's ability to regulate the ClC-Ka and ClC-Kb channels. (medlineplus.gov)
  • Analysis of lung gene expression reveals a role for Cl- channels in diisocyanate induced airway eosinophilia in a mouse model of asthma pathology. (cdc.gov)
  • CLCA1 (calcium-activated chloride channel regulator 1) was the most upregulated gene transcript (>100-fold) in all exposed mouse lungs versus controls, followed closely by SLC26A4, another transcript involved in Cl- conductance. (cdc.gov)
  • Crofelemer, a U.S. Food and Drug Administration-approved Cl- channel inhibitor, reduced MDI exposure induction of airway eosinophilia, mucus, CLCA1, and other asthma-associated gene transcripts. (cdc.gov)
  • When the report concerning chloride impermeability was published, efforts to find the gene were already well under way, terminating with a triumphant application of the techniques of reverse genetics. (rtmagazine.com)
  • Endophilin A2 regulates calcium-activated chloride channel activity via selective autophagy-mediated TMEM16A degradation. (bvsalud.org)
  • It also regulates the channels' stability and function. (medlineplus.gov)
  • Considering the molecular weight-function relationship of previously identified venom peptides, future bioactivity studies may lead to the discovery of novel potassium and chloride ion channel inhibitors as well as new antimicrobial peptides from L. abdullahbayrami venom. (scielo.br)
  • In 1983, Quinton and Bijman 4 clearly demonstrated the characteristic cellular defect of CF, which is epithelial chloride impermeability. (rtmagazine.com)
  • Evolving drugs include lubiprostone, which enhances colonic secretion by activating chloride channels. (lu.se)
  • The new study lays the groundwork for developing treatments for diseases such as asthma, COPD, cystic fibrosis, and even certain cancers," notes senior author Thomas J. Brett, Ph.D., assistant professor of medicine, and whose team's research report ("Secreted CLCA1 modulates TMEM16A to activate Ca 2+ -dependent chloride currents in human cells") appears in eLife. (genengnews.com)
  • Studies at the time suggested CLCA1 was an ion channel, a small opening in the cell membrane that allows charged particles to flow into or out of the cell. (genengnews.com)
  • Originally, CLCA1 was misidentified as a chloride channel," continues Dr. Brett. (genengnews.com)
  • When cells express CLCA1, they produce chloride currents. (genengnews.com)
  • Our results identify the first Cl− channel target of the CLCA family of proteins and establish CLCA1 as the first secreted direct modifier of TMEM16A activity, delineating a unique mechanism to increase currents," wrote the investigators. (genengnews.com)
  • We don't think that CLCA1 actually opens the channel," explains Dr. Brett. (genengnews.com)
  • In fact, the channel can function without CLCA1. (genengnews.com)
  • Mechanistically, ANO1 knockdown or pharmacological inhibition of its chloride-channel activity reduced EGF receptor (EGFR) and calmodulin-dependent protein kinase II (CAMKII) signaling, which subsequently attenuated AKT, v-src sarcoma viral oncogene homolog (SRC), and extracellular signal-regulated kinase (ERK) activation in vitro and in vivo. (nih.gov)
  • Only seven years ago, a protein that proved to be this elusive type of channel was first discovered in mammals. (genengnews.com)
  • We don't know of any other examples of this type of interaction between a protein and a channel. (genengnews.com)
  • According to Dr. Brett, his team is continuing to study these interactions to learn more about how increasing or decreasing expression of the protein or the channel may influence the currents, and what impact that may have in airway diseases. (genengnews.com)
  • This protein functions as a channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. (nih.gov)
  • In this study, we further characterized mouse tubuloids and differentiated them towards the collecting duct, which led to a significant upregulation of collecting duct-specific mRNAs of genes and protein expression, including the water channel AQP2 and the sodium channel ENaC. (frontiersin.org)
  • Calcium-activated chloride channel A4 (CLCA4) is known as a tumor suppressor which contributes to the progression of a number of types of malignant tumors. (medscimonit.com)
  • Our results highlight the involvement of the ANO1 chloride channel in tumor progression and provide insights into oncogenic signaling in human cancers with 11q13 amplification, thereby establishing ANO1 as a promising target for therapy in these highly prevalent tumor types. (nih.gov)
  • Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling. (nih.gov)
  • The calcium-activated chloride channel anoctamin 1 (ANO1) is located within the 11q13 amplicon, one of the most frequently amplified chromosomal regions in human cancer, but its functional role in tumorigenesis has remained unclear. (nih.gov)
  • In this study, the effects of calcium channel antagonists on the antidepressant action of alprazolam and imipramine were investigated. (who.int)
  • four groups each received a single dose of the calcium channel blocker followed by a single dose of the antidepressant (with same doses used for either in the previous four groups). (who.int)
  • This may be due to the fact that nifedipine on its own might act as an antidepressant but blocks one imipramine mechanism that depends on L-type calcium channel activation. (who.int)
  • The mouse FST for mental depression to investigate the effect of model has been widely used in screening the calcium channel blockers, nifedipine and antidepressants because it is simple and has been verapamil, on the antidepressant action of reported to be reliable across laboratories. (who.int)
  • We now used a genome-wide siRNA screen to molecularly identify the widely expressed acid-sensitive outwardly-rectifying anion channel PAORAC/ASOR. (elifesciences.org)
  • Molecular relation between anion channel and transporter: Evolutional insight of anion channel/transporter molecules. (nips.ac.jp)
  • On the flip side, these channel currents may be able to compensate for the genetic defect in cystic fibrosis, which causes mucus that is too thick and sticky. (genengnews.com)
  • Some mutations keep the channels from ever reaching the cell membrane. (medlineplus.gov)
  • Called TMEM16A, it is a channel that is ubiquitous in the cells lining the airway. (genengnews.com)
  • Based on therapeutic option, the global constipation treatment market has been segmented into laxatives, chloride channel activators, peripherally acting mu opioid receptor antagonists, GC-C agonists and 5-HT4 receptor agonists. (clickpress.com)
  • Elucidation of these roles has been greatly facilitated by the molecular identification of the underlying channel proteins, a discovery process that began in the late 1980's and is still ongoing. (elifesciences.org)
  • But as we became better at understanding the three-dimensional structures of proteins, researchers in the field started to realize that CLCA proteins couldn't be channels. (genengnews.com)
  • For example, TMEM16 channels and CLCA proteins have been associated with certain types of cancers, including breast tumors that spread to the lungs and in some cardiovascular disorders such as irregular heart rhythms and heart failure, demonstrating a possible broad impact of future work in this area. (genengnews.com)
  • Scorpion venoms are composed of inorganic salts, free amino acids, nucleotides, biogenic amines, peptides and proteins [ 4 Quintero-Hernández V, Jiménez-Vargas JM, Gurrola GB, Valdivia HH, Possani LD: Scorpion venom components that affect ion-channels function.Toxicon 2013,76:328-342. (scielo.br)
  • It is transmission of dopamine or NA decrease a highly specific antagonist of the L-type channel immobility, whereas agents having the opposite blocks [5]. (who.int)
  • Moreover, ANO1 chloride channel activity was important for cell viability. (nih.gov)
  • Barttin is essential for the normal placement of ClC-Ka and ClC-Kb channels in the cell membrane. (medlineplus.gov)
  • So the question arose, how do they activate these currents if they're not channels? (genengnews.com)
  • Acid-sensing ion channels have important functions in physiology and pathology, but the molecular composition of acid-activated chloride channels had remained unclear. (elifesciences.org)
  • In addition to chemokines and alternatively activated monocytes/macrophages, the data suggest a crucial role for Cl- channels in diisocyanate asthma pathology and as a possible target for intervention. (cdc.gov)
  • Kramer BK, Bergler T, Stoelcker B, Waldegger S. Mechanisms of Disease: the kidney-specific chloride channels ClCKA and ClCKB, the Barttin subunit, and their clinical relevance. (medlineplus.gov)
  • Based on the distribution channel, the global constipation treatment market is segmented into hospital pharmacies, retail pharmacies and online pharmacies. (clickpress.com)
  • These channels are necessary for the normal function of organs such as the lungs and pancreas. (nih.gov)
  • Barttin is a Cl- channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion. (medlineplus.gov)
  • Antihypertensive DHPs act by blocking L-type voltage-dependent Ca++ channels and therefore cause the relaxation of arterial smooth muscle cells. (units.it)
  • We think it simply keeps the channel on the surface of the cells for a longer period of time. (genengnews.com)
  • Differentiation resulted in polarized expression of collecting duct water channels AQP2 and AQP3. (frontiersin.org)