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.
Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.
A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.
A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.
Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.
A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of CARDIOMYOCYTES. Defects in the SCN5A gene, which codes for the alpha subunit of this sodium channel, are associated with a variety of CARDIAC DISEASES that result from loss of sodium channel function.
A voltage-gated sodium channel subtype that mediates the sodium ion permeability of excitable membranes. Defects in the SCN2A gene which codes for the alpha subunit of this sodium channel are associated with benign familial infantile seizures type 3, and early infantile epileptic encephalopathy type 11.
A voltage-gated sodium channel subtype found widely expressed in neurons of the central and peripheral nervous systems. Defects in the SCN8A gene which codes for the alpha subunit of this sodium channel are associated with ATAXIA and cognitive deficits.
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.
Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.
A family of membrane proteins that selectively conduct SODIUM ions due to changes in the TRANSMEMBRANE POTENTIAL DIFFERENCE. They typically have a multimeric structure with a core alpha subunit that defines the sodium channel subtype and several beta subunits that modulate sodium channel activity.
A voltage-gated sodium channel subtype that is expressed in nociceptors, including spinal and trigeminal sensory neurons. It plays a role in the transmission of pain signals induced by cold, heat, and mechanical stimuli.
A class of drugs that stimulate sodium influx through cell membrane channels.
A voltage-gated sodium channel subtype that is predominantly expressed in the CENTRAL NERVOUS SYSTEM. Defects in the SCN1A gene which codes for the alpha subunit of this sodium channel are associated with DRAVET SYNDROME, generalized epilepsy with febrile seizures plus, type 2 (GEFS+2), and familial hemiplegic migraine type 3.
A voltage-gated sodium channel subtype found widely expressed in nociceptive primary sensory neurons. Defects in the SCN9A gene, which codes for the alpha subunit of this sodium channel, are associated with several pain sensation-related disorders.
A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of SKELETAL MYOCYTES. Defects in the SCN4A gene, which codes for the alpha subunit of this sodium channel, are associated with several MYOTONIC DISORDERS.
A compound that contains a reduced purine ring system but is not biosynthetically related to the purine alkaloids. It is a poison found in certain edible mollusks at certain times; elaborated by GONYAULAX and consumed by mollusks, fishes, etc. without ill effects. It is neurotoxic and causes RESPIRATORY PARALYSIS and other effects in MAMMALS, known as paralytic SHELLFISH poisoning.
Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.
Batrachotoxin is the 20-alpha-bromobenzoate of batrachotoxin A; they are toxins from the venom of a small Colombian frog, Phyllobates aurotaenia, cause release of acetylcholine, destruction of synaptic vesicles and depolarization of nerve and muscle fibers.
A voltage-gated sodium channel subtype found in neuronal tissue that mediates the sodium ion PERMEABILITY of excitable membranes.
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 class of drugs that act by selective inhibition of calcium influx through cellular membranes.
An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.
A 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.
Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.
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.
A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS.
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).
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).
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.
The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.
Venoms from animals of the order Scorpionida of the class Arachnida. They contain neuro- and hemotoxins, enzymes, and various other factors that may release acetylcholine and catecholamines from nerve endings. Of the several protein toxins that have been characterized, most are immunogenic.
A voltage-gated sodium channel subtype found in the neurons of the NERVOUS SYSTEM and DORSAL ROOT GANGLIA. It may play a role in the generation of heat and mechanical pain hypersensitivity.
Potassium channel whose permeability to ions is extremely sensitive to the transmembrane potential difference. The opening of these channels is induced by the membrane depolarization of the ACTION POTENTIAL.
A benzoate-cevane found in VERATRUM and Schoenocaulon. It activates SODIUM CHANNELS to stay open longer than normal.
A voltage-gated sodium channel beta subunit abundantly expressed in SKELETAL MUSCLE; HEART; and BRAIN. It non-covalently associates with voltage-gated alpha subunits. Defects in the SCN1B gene, which codes for this beta subunit, are associated with generalized epilepsy with febrile seizures plus, type 1, and Brugada syndrome 5.
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.
The ability of a substrate to allow the passage of ELECTRONS.
A subclass of sodium channel blockers that are specific for EPITHELIAL SODIUM CHANNELS.
Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.
A family of mechanosensitive sodium channels found primarily in NEMATODES where they play a role in CELLULAR MECHANOTRANSDUCTION. Degenerin sodium channels are structurally-related to EPITHELIAL SODIUM CHANNELS and are named after the fact that loss of their activity results in cellular degeneration.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
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.
Compounds that either stimulate the opening or prevent closure of EPITHELIAL SODIUM ION CHANNELS.
Potassium channels whose activation is dependent on intracellular calcium concentrations.
A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.
The rate dynamics in chemical or physical systems.
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 voltage-gated sodium channel beta subunit subtype that non-covalently associates with voltage-gated alpha subunits. Defects in the SCN3B gene which codes for this beta subunit are associated with Brugada syndrome 7.
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.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.
Regularly spaced gaps in the myelin sheaths of peripheral axons. Ranvier's nodes allow saltatory conduction, that is, jumping of impulses from node to node, which is faster and more energetically favorable than continuous conduction.
The active insecticidal constituent of CHRYSANTHEMUM CINERARIIFOLIUM flowers. Pyrethrin I is the pyretholone ester of chrysanthemummonocarboxylic acid and pyrethrin II is the pyretholone ester of chrysanthemumdicarboxylic acid monomethyl ester.
CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.
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.
Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties.
Sodium or sodium compounds used in foods or as a food. The most frequently used compounds are sodium chloride or sodium glutamate.
Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.
A 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 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 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.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
A 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.
Peptide neurotoxins from the marine fish-hunting snails of the genus CONUS. They contain 13 to 29 amino acids which are strongly basic and are highly cross-linked by disulfide bonds. There are three types of conotoxins, omega-, alpha-, and mu-. OMEGA-CONOTOXINS inhibit voltage-activated entry of calcium into the presynaptic membrane and therefore the release of ACETYLCHOLINE. Alpha-conotoxins inhibit the postsynaptic acetylcholine receptor. Mu-conotoxins prevent the generation of muscle action potentials. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)
A voltage-gated sodium channel beta subunit subtype that covalently associates with voltage-gated alpha subunits. Defects in the SCN4B gene, which codes for this beta subunit, are associated with long QT syndrome-10.
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.
Insects of the order Dictyoptera comprising several families including Blaberidae, BLATTELLIDAE, Blattidae (containing the American cockroach PERIPLANETA americana), Cryptocercidae, and Polyphagidae.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
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 delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.
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.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A voltage-gated sodium channel beta subunit that binds covalently to voltage-gated alpha subunits.
Established cell cultures that have the potential to propagate indefinitely.
A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.
A ubiquitous sodium salt that is commonly used to season food.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.
Arthropods of the order Scorpiones, of which 1500 to 2000 species have been described. The most common live in tropical or subtropical areas. They are nocturnal and feed principally on insects and other arthropods. They are large arachnids but do not attack man spontaneously. They have a venomous sting. Their medical significance varies considerably and is dependent on their habits and venom potency rather than on their size. At most, the sting is equivalent to that of a hornet but certain species possess a highly toxic venom potentially fatal to humans. (From Dorland, 27th ed; Smith, Insects and Other Arthropods of Medical Importance, 1973, p417; Barnes, Invertebrate Zoology, 5th ed, p503)
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 commonly mutated in human episodic ATAXIA and MYOKYMIA.
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.
Compounds based on an 8-membered heterocyclic ring including an oxygen. They can be considered medium ring ethers.
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.
A superorder of CEPHALOPODS comprised of squid, cuttlefish, and their relatives. Their distinguishing feature is the modification of their fourth pair of arms into tentacles, resulting in 10 limbs.
Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain.
Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.
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.
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.
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.
Toxic or poisonous substances elaborated by marine flora or fauna. They include also specific, characterized poisons or toxins for which there is no more specific heading, like those from poisonous FISHES.
Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of MYOTONIC DISORDERS.
A voltage-gated potassium channel that is expressed primarily in the HEART.
Synthetic transcripts of a specific DNA molecule or fragment, made by an in vitro transcription system. This cRNA can be labeled with radioactive uracil and then used as a probe. (King & Stansfield, A Dictionary of Genetics, 4th ed)
A 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.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
A set of protein subcomplexes involved in PROTEIN SORTING of UBIQUITINATED PROTEINS into intraluminal vesicles of MULTIVESICULAR BODIES and in membrane scission during formation of intraluminal vesicles, during the final step of CYTOKINESIS, and during the budding of enveloped viruses. The ESCRT machinery is comprised of the protein products of Class E vacuolar protein sorting genes.
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.
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.
Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate.
Venoms from jellyfish; CORALS; SEA ANEMONES; etc. They contain hemo-, cardio-, dermo- , and neuro-toxic substances and probably ENZYMES. They include palytoxin, sarcophine, and anthopleurine.
Proteins obtained from species in the class of AMPHIBIANS.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Elements of limited time intervals, contributing to particular results or situations.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A 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.
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.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.
A genus of fish, in the family GYMNOTIFORMES, capable of producing an electric shock that immobilizes fish and other prey. The species Electrophorus electricus is also known as the electric eel, though it is not a true eel.
A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN repeats are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES.
A peripheral arterial disease that is characterized by the triad of ERYTHEMA, burning PAIN, and increased SKIN TEMPERATURE of the extremities (or red, painful extremities). Erythromelalgia may be classified as primary or idiopathic, familial or non-familial. Secondary erythromelalgia is associated with other diseases, the most common being MYELOPROLIFERATIVE DISORDERS.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
Polycyclic ethers produced by Gambierdiscus (DINOFLAGELLATES) from gambiertoxins, which are ingested by fish which in turn may be ingested by humans who are susceptible to the CIGUATERA POISONING.
Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.
The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.
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.
Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.
Ishibashi K, Marumo F (June 1998). "Molecular cloning of a DEG/ENaC sodium channel cDNA from human testis". Biochem. Biophys. ... Acid-sensing ion channel 3 (ASIC3) also known as amiloride-sensitive cation channel 3 (ACCN3) or testis sodium channel 1 (TNaC1 ... Hanukoglu I (2017). "ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity ... Hanukoglu I, Hanukoglu A (Jan 2016). "Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue ...
... inhibits the epithelial sodium channel (ENaC), and also has anti-microbial functions. As such, plunc is believed to play ... PLUNC+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from ... This gene is the human homolog of murine plunc, and like the mouse gene, is specifically expressed in the airways and ... Ghafouri B, Kihlström E, Tagesson C, Lindahl M (Jun 2004). "PLUNC in human nasal lavage fluid: multiple isoforms that bind to ...
"Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages". Histochemistry and ... In humans[edit]. In humans, it goose bumps can even extend to piloerection as a reaction to hearing nails scratch on a ... In humans, goose bumps are strongest on the forearms,[citation needed] but also occur on the legs, neck, and other areas of the ... The formation of goose bumps in humans under stress is considered to be a vestigial reflex;[2] and its function in other apes ...
"Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages". Histochemistry and ... ion channels, ENaC and CFTR (see Fig. 6 and Fig. 7 in reference[7]). ... Thiboutot, D (July 2004). "Regulation of human sebaceous glands". The Journal of Investigative Dermatology. 123 (1): 1-12. doi: ... The sebaceous glands of a human fetus secrete a substance called vernix caseosa, a waxy, translucent white substance coating ...
"Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages". Histochemistry and ... through both calcium-sensitive chloride channels[16] and voltage-independent cation channels permeable to calcium.[17] Moreover ... This article is about human skin. For the outer layer of cells in plants, see Epidermis (botany). For other uses, see Epidermis ... Cellular mechanisms for regulating water and sodium levels (ENaCs) are found in all layers of the epidermis.[5] ...
"Delta-subunit confers novel biophysical features to alpha beta gamma-human epithelial sodium channel (ENaC) via a physical ... The SCNN1D gene encodes for the δ (delta) subunit of the epithelial sodium channel ENaC in vertebrates. ENaC is assembled as a ... As ENaC is strongly inhibited by amiloride, it is also referred to as an "amiloride-sensitive sodium channel". The first cDNA ... ENaC is expressed in epithelial cells and is different from the voltage-gated sodium channel that is involved in the generation ...
"BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels ... Hanukoglu I (2017). "ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity ... Acid-sensing ion channel 2 (ASIC2) also known as amiloride-sensitive cation channel 1, neuronal (ACCN1) or brain sodium channel ... with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel)". The Biochemical ...
Hanukoglu I (2017). "ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity ... Acid-sensing ion channel 4 (ASIC4) also known as amiloride-sensitive cation channel 4 (ACCN4) is a protein that in humans is ... Hanukoglu I, Hanukoglu A (Jan 2016). "Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue ... This gene encodes a member of the ASIC/ENaC superfamily of proteins. The members of this family are amiloride-sensitive sodium ...
"BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels ... Hanukoglu I (2017). "ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity ... Acid-sensing ion channel 1 (ASIC1) also known as amiloride-sensitive cation channel 2, neuronal (ACCN2) or brain sodium channel ... with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel)". Biochem. J. 361 (Pt ...
"Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages". Histochemistry and ... In contrast, ENaC (Epithelial sodium channel) is located along the entire length of the cilia. In sweat glands, defective CFTR ... Sharma S, Hanukoglu I (April 2019). "Mapping the sites of localization of epithelial sodium channel (ENaC) and CFTR in segments ... Sharma S, Hanukoglu A, Hanukoglu I (April 2018). "Localization of epithelial sodium channel (ENaC) and CFTR in the germinal ...
"Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages". Histochemistry and ... In the sweat ducts, the Na+ ions are re-absorbed into tissue by epithelial sodium channels (ENaC) that are located on the ... In a cool climate and in the absence of exercise, sodium loss can be very low (less than 5 mmol/d). Sodium concentration in ... In humans, sweat is hypoosmotic relative to plasma (i.e. less concentrated). Sweat is found at moderately acidic to neutral pH ...
"Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages". Histochemistry and ... The Na+ ions are re-absorbed into the tissue via the epithelial sodium channels (ENaC) that are located on the apical membrane ... Hanukoglu I, Hanukoglu A (Jan 2016). "Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue ... "Truncated beta epithelial sodium channel (ENaC) subunits responsible for multi-system pseudohypoaldosteronism (PHA) support ...
"Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages". Histochemistry and ... through both calcium-sensitive chloride channels and voltage-independent cation channels permeable to calcium. Moreover, it has ... The human epidermis is a familiar example of epithelium, particularly a stratified squamous epithelium The word epidermis is ... Tu, CL; Oda, Y; Bikle, DD (1999). "Effects of a calcium receptor activator on the cellular response to calcium in human ...
Sharma S, Hanukoglu A, Hanukoglu I (2018). "Localization of epithelial sodium channel (ENaC) and CFTR in the germinal ... In humans the mechanism is not completely understood; however it is known that initiation of spermatogenesis occurs at puberty ... For humans, the entire process of spermatogenesis is variously estimated as taking 74 days (according to tritium-labelled ... In humans, chromosomal abnormalities arising from incorrect spermatogenesis results in congenital defects and abnormal birth ...
Epithelial sodium channels ENaC that are specifically expressed along the entire length of cilia apparently serve as sensors ... Its importance to human biology has been underscored by the discovery of its role in a diverse group of diseases caused by the ... As noted above, epithelial sodium channels ENaC that are expressed along the length of cilia regulate fluid level surrounding ... Hanukoglu I, Hanukoglu A (April 2016). "Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue ...
"Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages". Histochemistry and ... In the sweat ducts, the Na+ ions are re-absorbed into tissue by epithelial sodium channels (ENaC) that are located on the ... In a cool climate and in the absence of exercise, sodium loss can be very low (less than 5 mmol/d). Sodium concentration in ... Jessen, C. (2000). Temperature Regulation in Humans and Other Mammals. Berlin: Springer. ISBN 978-3-540-41234-2. .. ...
This sodium channel is known as an epithelial sodium channel (ENaC) and is composed of three subunits. An ENaC can be blocked ... "Relaxation Of Selective Constraint And Loss Of Function In The Evolution Of Human Bitter Taste Receptor Genes". Human Molecular ... A sodium channel in the taste cell wall allows sodium cations to enter the cell. This on its own depolarizes the cell, and ... The receptor for amiloride-sensitive attractive salty taste in mice has been shown to be a sodium channel. There is some ...
"Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages". Histochemistry and ... that encode for protein subunits of the Epithelial sodium (Na+) channel (ENaC). These studies also helped establish that ENaC ... Hanukoglu I (August 2016). "ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity ... Enuka Y, Hanukoglu I, Edelheit O, Vaknine H, Hanukoglu A (March 2012). "Epithelial sodium channels (ENaC) are uniformly ...
"Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages". Histochemistry and ... Jessen, C. (2000). Temperature Regulation in Humans and Other Mammals. Berlin: Springer. ISBN 3-540-41234-4. .. ... Mack, G. W.; Nadel, E. R. (1996). "Body fluid balance during heat stress in humans". Dalam Fregly, M. J.; Blatteis, C. M. (para ...
Sharma S, Hanukoglu I (2019). "Mapping the sites of localization of epithelial sodium channel (ENaC) and CFTR in segments of ... The male reproductive system consists of a number of sex organs that play a role in the process of human reproduction. These ... "Localization of epithelial sodium channel (ENaC) and CFTR in the germinal epithelium of the testis, Sertoli cells, and ... The gene for sexual differentiation in humans, called the testis determining factor (TDF), is located on the short arm of the Y ...
2003). "The transmembrane serine protease (TMPRSS3) mutated in deafness DFNB8/10 activates the epithelial sodium channel (ENaC ... Transmembrane protease, serine 3 is an enzyme that in humans is encoded by the TMPRSS3 gene. This gene encodes a member of the ... 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957-68. doi: ... Serine proteases are known to be involved in a variety of biological processes, whose malfunction often leads to human diseases ...
The SCNN1B gene encodes for the β subunit of the epithelial sodium channel ENaC in vertebrates. ENaC is assembled as a ... and gamma-subunits of the human ENaC. The exon-intron organization of the human beta ENaC gene SCNN1B was determined by Saxena ... As ENaC is strongly inhibited by amiloride, it is also referred to as an "amiloride-sensitive sodium channel". The first cDNA ... ENaC is expressed in epithelial cells and is different from the voltage-gated sodium channel that is involved in the generation ...
The primary targets of NEDD4-2 include the epithelial sodium channel (ENaC), the Na+-Cl- co-transporter (NCC), and the voltage ... In human the protein is encoded by the NEDD4L gene. In mouse the protein is commonly known as NEDD4-2 and the gene Nedd4-2. ... individual epithelial sodium channel subunits and reduce surface expression and function of the epithelial sodium channel". Am ... NEDD4-2 has been shown to ubiquitinate and therefore down regulate the epithelial sodium channel (ENaC) in the collecting ducts ...
... subunits of the Epithelial sodium channel ENaC. These mutations abrogate the binding to the ubiquitin ligase NEDD4, thereby ... Viruses often mimic human SLiMs to hijack and disrupt a host's cellular machinery, thereby adding functionality to their ... January 2005). "Liddle's syndrome caused by a novel mutation in the proline-rich PY motif of the epithelial sodium channel beta ... inhibiting channel degradation and prolonging the half-life of ENaC, ultimately resulting in increased Na+ reabsorption, plasma ...
In a systematic study on the roles of conserved charged residues on the surface of epithelial sodium channel (ENaC), alanine ... was used to determine simultaneously the functional contributions of 19 side chains buried at the interface between human ... "Identification of the roles of conserved charged residues in the extracellular domain of an epithelial sodium channel (ENaC) ...
"Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages". Histochemistry and ... The SCNN1A gene encodes for the α subunit of the epithelial sodium channel ENaC in vertebrates. ENaC is assembled as a ... As ENaC is strongly inhibited by amiloride, it is also referred to as an "amiloride-sensitive sodium channel". The first mRNA ... ENaC is expressed in epithelial cells and is different from the voltage-gated sodium channel that is involved in the generation ...
Boggula VR, Hanukoglu I, Sagiv R, Enuka Y, Hanukoglu A (October 2018). "Expression of the epithelial sodium channel (ENaC) in ... Sloboda, D. M.; Hickey, M.; Hart, R. (2010). "Reproduction in females: the role of the early life environment". Human ... Omberlet, W. (2012). "Global access to infertility care in developing countries: a case of human rights, equity and social ... Human Reproduction Update. 19 (1): 12-25. doi:10.1093/humupd/dms032. PMID 22899657. Codner, E.; Merino, P. M.; Tena-Sempere, M ...
Hanukoglu I (2017). "ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity ... channel from human small intestine". FEBS Letters. 471 (2-3): 205-10. doi:10.1016/s0014-5793(00)01403-4. PMID 10767424. ... Hanukoglu I, Hanukoglu A (Jan 2016). "Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue ... This gene encodes a member of the ASIC/ENaC superfamily of proteins. The members of this family are amiloride-sensitive sodium ...
The SCNN1G gene encodes for the γ subunit of the epithelial sodium channel ENaC in vertebrates. ENaC is assembled as a ... "Human Nedd4 interacts with the human epithelial Na+ channel: WW3 but not WW1 binds to Na+-channel subunits". Biochem. J. 345 (3 ... As ENaC is strongly inhibited by amiloride, it is also referred to as an "amiloride-sensitive sodium channel". The first cDNA ... ENaC is expressed in epithelial cells and is different from the voltage-gated sodium channel that is involved in the generation ...
... is a member of the sodium channel blocking class of antiepileptic drugs.[60] This may suppress the release of ... It is known that lamotrigine is a weak inhibitor of human dihydrofolate reductase (DHFR) and other, more powerful, human DHFR ... It is a triazine derivate that inhibits voltage-sensitive sodium channels, leading to stabilization of neuronal membranes. It ... As is the case for antiepileptic drugs that act on voltage-dependent sodium channels, lamotrigine thereby inhibits the release ...
Jan Riordan (January 2005). Breastfeeding and Human Lactation. Jones & Bartlett Learning. pp. 76-. ISBN 978-0-7637-4585-1.. ... The cause is thought to be blockade of hERG voltage-gated potassium channels.[41][42] The risks are dose-dependent, and appear ... In the United States, domperidone is not currently a legally marketed human drug and it is not approved for sale in the U.S. On ... Chang SY, Fancher RM, Zhang H, Gan J (2010). "Mechanism-based inhibition of human cytochrome P4503A4 by domperidone". ...
... is a sodium channel blocker.[28] It binds preferentially to voltage-gated sodium channels in their inactive ... Prosser RS, Sibley PK (February 2015). "Human health risk assessment of pharmaceuticals and personal care products in plant ... Ion channel blockers. *Anticonvulsants (e.g., gabapentin, pregabalin, mirogabalin, carbamazepine, oxcarbazepine, lacosamide, ... and calcium channel blockers.[12] Carbamazepine also increases the metabolism of the hormones in birth control pills and can ...
They render channel activity responsive to the cytoplasmic ATP/ADP ratio (increased ATP/ADP closes the channel). The human SUR1 ... Inward-rectifier potassium channels (Kir, IRK) are a specific subset of potassium channels. To date, seven subfamilies have ... Classification of Kir channels[edit]. There are seven subfamilies of Kir channels, denoted as Kir1 - Kir7.[1] Each subfamily ... Role of Kir channels[edit]. Kir channels are found in multiple cell types, including macrophages, cardiac and kidney cells, ...
Sharma S, Hanukoglu I (2019). "Mapping the sites of localization of epithelial sodium channel (ENaC) and CFTR in segments of ... Reproductive system of the human male. This article is about the reproductive system in human males. For the male reproductive ... Sharma S, Hanukoglu A, Hanukoglu I (2018). "Localization of epithelial sodium channel (ENaC) and CFTR in the germinal ... Wikimedia Commons has media related to Human male reproductive system.. *This article incorporates text in the public domain ...
SCN4A is an important component of sodium channels in skeletal muscles. During exercise, sodium channels would open to allow ... Herlihy, Barbara (2014). The Human Body in Health and Illness. Elsevier Health Sciences. p. 487. ISBN 9781455756421. Archived ... whereas the ENaC itself is blocked not only by amiloride and triamterene but also by trimethoprim and pentamidine.. ... But in hyperkalemic periodic paralysis, sodium channels are slow to close after exercise, causing excessive influx of sodium ...
It has been shown that epithelial sodium channel ENaC that allows the flow of Na+ ions into the cell is localized on ... Adult human testicle with epididymis: A. Head of epididymis, B. Body of epididymis, C. Tail of epididymis, and D. Vas deferens ... Sharma S, Hanukoglu I (2019). "Mapping the sites of localization of epithelial sodium channel (ENaC) and CFTR in segments of ... It is a single, narrow, tightly-coiled tube in adult humans, 6 to 7 meters (20 to 23 ft) in length[1] connecting the efferent ...
CYP2C9 is involved in the formation of hydroxygliclazide in human liver microsomes and in a panel of recombinant human P450s in ... This causes voltage dependent Ca2+ ion channels to open increasing the Ca2+ influx. The calcium can then bind to and activate ... found that human MODY patients respond differently and that there was no consistent decrease in gliclazide clearance in ... 2015). "Half-Life of Sulfonylureas in HNF1A and HNF4A Human MODY Patients is not Prolonged as Suggested by the Mouse Hnf1a-/- ...
It works as a non-selective voltage-gated sodium channel blocker and belongs to the Class IB group of anti-arrhythmic ... Mexiletine is available for human use in the US, and has been reintroduced in the UK as a licensed product, having previously ... The LQT3 form of long QT syndrome is amenable to treatment with mexiletine as this form is caused by defective sodium channels ... Ion channel blockers. *Anticonvulsants (e.g., gabapentin, pregabalin, mirogabalin, carbamazepine, oxcarbazepine, lacosamide, ...
Sharma S, Hanukoglu I (2019). "Mapping the sites of localization of epithelial sodium channel (ENaC) and CFTR in segments of ... "American Journal of Human Genetics. 84 (5): 617-627. doi:10.1016/j.ajhg.2009.04.007. PMC 2680995. PMID 19409525.. ... The structure periodicity may also regulate the sodium ion channels in axons. ... "American Journal of Human Genetics. 78 (6): 947-960. doi:10.1086/504271. PMC 1474101. PMID 16685646.. ...
上皮組織鈉通道(英语:Epithelial sodium channel)(ENaC)的Alpha亞基. 無義突變導致女性生殖道ENaC的基因表現缺損[39] ... Human Reproduction Update. 2002, 8 (2): 141-154. ISSN 1355-4786. PMID 12099629. doi:10.1093/humupd/8.2.141.. ... Boggula VR, Hanukoglu I, Sagiv R, Enuka Y, Hanukoglu A. Expression of the epithelial sodium channel (ENaC) in the endometrium ... Human Reproduction Update. 2014, 20 (5): 688-701. ISSN 1355-4786. PMID 24821925. doi
The mechanism of action of phenytoin sodium. Sodium channels are: 1) Closed 2) Open 3) Inactive (phenytoin effect) ... There is no good evidence that phenytoin is a human carcinogen.[27][28] ... Phenytoin is believed to protect against seizures by causing voltage-dependent block of voltage gated sodium channels.[38] This ... Sodium channels exist in three main conformations: the resting state, the open state, and the inactive state. ...
... including the three subunits of the epithelial sodium channel (ENaC), the Na+/K+ pumps and their regulatory proteins serum and ... Voltage-gated Ca2+ channels have been detected in the zona glomerulosa of the human adrenal, which suggests that Ca2+ channel ... Aldosterone upregulates epithelial sodium channels (ENaCs) in the collecting duct and the colon, increasing apical membrane ... The plasma concentration of sodiumEdit. Aldosterone levels vary as an inverse function of sodium intake as sensed via osmotic ...
... leading to increased expression of the epithelial sodium channel (ENaC), which also promotes sodium re absorption. WNK1 ... "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. "Mouse PubMed ... and large conductance calcium-activated potassium channel (BKCa) are the two primary channels for potassium secretion. WNK1 ... In the distal convoluted tubule (DCT), WNK1 is a potent activator of the NCC that results in an increase in sodium re ...
Na+/K+ ATPase pump at the basolateral membrane and Na+ channel called ENaC, located at the apical membrane of the renal tubule ... They decrease sodium reabsorption which leads to increased water excretion by the kidneys. By regulating water excretion, ... This protein has high affinity for aldosterone but also for cortisol in humans and corticosterone in mice and rats. For this ... In those times, the main use of aldosterone was recognized as the control of renal sodium and the excretion of potassium. Hans ...
About 20 percent can be accredited to the epithelial sodium channel. Protoelyzed variants of ENaC also function as human salt ... The epithelial sodium channel (short: ENaC, also: amiloride-sensitive sodium channel) is a membrane-bound ion channel that is ... and are also thought to form sodium channels. The epithelial sodium (Na+ ) channel (ENaC) family belongs to the ENaC/P2X ... "Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages". Histochemistry and ...
... dimerise to form a functional channel. Hanukoglu I, Hanukoglu A (April 2016). "Epithelial sodium channel (ENaC) family: ... Equine hyperkalaemic periodic paralysis as well as human hyperkalaemic periodic paralysis (HyperPP) are caused by a defect in ... Sodium channels Voltage-gated sodium channels (NaVs) Epithelial sodium channels (ENaCs) Calcium channels (CaVs) Proton channels ... Plasma membrane channels Examples: Voltage-gated potassium channels (Kv), Sodium channels (Nav), Calcium channels (Cav) and ...
Amiloride works by directly blocking the epithelial sodium channel (ENaC) thereby inhibiting sodium reabsorption in the distal ... "Intracellular Ca2+ mediates the cytotoxicity induced by bepridil and benzamil in human brain tumor cells". Cancer Letters. 88 ( ... Benzamil or benzyl amiloride is a potent blocker of the ENaC channel and also a sodium-calcium exchange blocker. It is a potent ... Chalfant, M.L. (1995). "Regulation of epithelial Na+ channels from M-1 cortical collecting duct cells". American Journal of ...
Ishibashi K, Marumo F (June 1998). "Molecular cloning of a DEG/ENaC sodium channel cDNA from human testis". Biochem. Biophys. ... Acid-sensing ion channel 3 (ASIC3) also known as amiloride-sensitive cation channel 3 (ACCN3) or testis sodium channel 1 (TNaC1 ... Hanukoglu I (2017). "ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity ... Hanukoglu I, Hanukoglu A (Jan 2016). "Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue ...
Plunc inhibits the epithelial sodium channel (ENaC), and also has anti-microbial functions. As such, plunc is believed to play ... PLUNC+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from ... This gene is the human homolog of murine plunc, and like the mouse gene, is specifically expressed in the airways and ... Ghafouri B, Kihlström E, Tagesson C, Lindahl M (Jun 2004). "PLUNC in human nasal lavage fluid: multiple isoforms that bind to ...
Inhibitor of the amiloride-sensitive Epithelial Sodium Channel (ENaC) ... AZD5634 is a potent inhibitor of the epithelial sodium channel in human, sheep and rat in vitro with an IC50 of 3.8 nmol/L for ... Thus, its inhibitory effects at ENaC are long lasting. Its effects at the NHE-channels have not been explored. ... the human ENaC. AZD5634 is designed to have a long duration at the target and at the apical side of the airways. ...
"Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages", "Sweat gland function ... In the sweat ducts, the Na+ ions are re-absorbed into tissue by epithelial sodium channels (ENaC) that are located on the ... In the sweat ducts, the Na+ ions are re-absorbed into tissue by epithelial sodium channels (ENaC) that are located on the ... Human eccrine sweat is essentially a dilute sodium chloride solution with trace amounts of other plasma electrolytes. Be on the ...
Aberrantly filtered plasmin in urine may activate proteolytically the γ-subunit of the epithelial sodium channel (ENaC) and ... α-ENaC, and renal outer medullary K-channel (ROMK) and compared with human kidney cortex homogenate. Urine total plasmin(ogen) ... Aberrantly filtered plasmin in urine may activate proteolytically the γ-subunit of the epithelial sodium channel (ENaC) and ... Aberrantly filtered plasmin in urine may activate proteolytically the γ-subunit of the epithelial sodium channel (ENaC) and ...
identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. [15] The cells and peripheral representation of ... 1.6 Human Weekly Development - Two Prominent Studies *1.6.1 Timeline of Developmental Processes of the Gustatory System ... Human Weekly Development - Two Prominent Studies. Martin Witt and Klaus Reutter of the University of Tubingen in Germany ... discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). [13] The Cells and Logic ...
... plays a critical role in epithelial sodium transport by regulating the cell surface expression of the epithelial sodium channel ... This summary is for the human ortholog.] This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. ... ENaC. Single nucleotide polymorphisms in this gene may be associated with essential hypertension. Alternatively spliced ...
Camostat is a trypsin-like protease inhibitor and inhibits airway epithelial sodium channel (ENaC) function.. Approved/ ...
ENaC; IC50 = 4.5 µM for the rat channel). In vivo, triamterene (0.5-32 mg/animal) enhances sodium secretion and decreases ... Triamterene is an inhibitor of the epithelial sodium channel ( ... Triamterene is an inhibitor of the epithelial sodium channel ( ... ENaC; IC50 = 4.5 µM for the rat channel). In vivo, triamterene (0.5-32 mg/animal) enhances sodium secretion and decreases ...
vc_row][vc_column][vc_column_text]VX-371 (formerly P-1037) is an inhaled epithelial sodium channel (ENaC) inhibitor being ... An in vitro study showed that VX-371 had a change in cilia beat frequency when used in combination with Orkambi in human ... that blocks the sodium channel in airway cells. By blocking this channel, VX-371 may prolong the duration and maintenance of ...
... how SARS-CoV-2 enters the airways during the early stages of infection and the possible role of epithelial sodium channels ( ... The COVID Human Genetic Effort is an international consortium of scientists around the world aiming to discover genetic ... ENaC) in the process. This opinion paper was published in the journal FUNCTION. ... Giuseppe Novelli MAE is part of the COVID Human Genetic Effort and co-author of the paper Life-threatening COVID-19: defective ...
... how SARS-CoV-2 enters the airways during the early stages of infection and the possible role of epithelial sodium channels ( ... The COVID Human Genetic Effort is an international consortium of scientists around the world aiming to discover genetic ... ENaC) in the process. This opinion paper was published in the journal FUNCTION. ... Giuseppe Novelli MAE is part of the COVID Human Genetic Effort and co-author of the paper Life-threatening COVID-19: defective ...
The sodium chloride cotransporter (NCC) and epithelial sodium channel (ENaC) associate. Biochemical Journal. 473:3237-3252. ... Signaling network crosstalk in human pluripotent cells: A Smad2/3-regulated switch that controls the balance between self- ... and function of macromolecular complexes in cellular communication and providing insight into the cellular basis for human ...
Ph.D.forsvar: Carolina Graffe "Urinary excretion of aquaporin-2 and beta subunit of the epithelial sodium channel in healthy ... Role of ENaC in NaCl retention and hypertension in proteinuric disease. Boye L. Jensen (Foredragsholder) ... Human kidney tissue collection - The COX project a 10-year celebration. Boye L. Jensen (Foredragsholder) ... ENaC - a new culprit in the pathophysiology of preeclampsia. Boye L. Jensen (Foredragsholder) ...
sodium will become this to be your Colonies better. expansion will manufacture this to differ your group better. request will ... growing Human: current way and the century of Freedom. Westlinning, Margot( 1995). Logic and the standards of the field, ... The site contributes using the processing of channel writing to thymic student of insecurity in the very aim and markets in the ... ENaC) and its involved sanitation of K+ do Fixed by drive. 39 What is all this download Medical X Ray, Electron Beam, and Gamma ...
Keywords: bolt-channel numerical simulation popular lock aluminium profile Abstract Download PDF Download RIS Download Bibtex ... Keywords: Foundry engineering ablation casting Moulding sands hydrated sodium silicate hot-box technology ... 46 Effect of increased temperature on dimensional and shape accuracy of castings produced from the EN AC-AlSi11 alloy by ... In presented work the effects of chemical agents on plates of human fingernails were studied using Atomic Force Microscopy and ...
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  • SCNN1B (Sodium Channel Epithelial 1 Subunit Beta) is a Protein Coding gene. (genecards.org)
  • The SCNN1G gene provides instructions for making one piece, the gamma subunit, of a protein complex called the epithelial sodium channel (ENaC). (medlineplus.gov)
  • The RGZ-induced Iam increase was not mediated through direct serum- and glucocorticoid-regulated kinase (SGK1)-dependent phosphorylation of serine residue 594 on the human ENaC α-subunit but by the diminution of ENaC ubiquitination through the SGK1/Nedd4-2 pathway. (deepdyve.com)
  • The membrane topology of each subunit predicts the presence of two transmembrane domains (M1 and M2), a large extracellular loop (~70% of the size of the channel) and relatively short amino and carboxyl termini. (intechopen.com)
  • ENaC subunits form heterotrimeric complexes that function as constitutively active Na + channels, with different subunit composition resulting in channels with distinct kinetics. (jcancer.org)
  • The α -subunit is required for Na + conductance while β - and γ -subunits are needed to enhance the channel activity ( Warnock & Rossier , 2005 ). (peerj.com)
  • In Liddle's syndrome, a form of hypertension caused by an increase in the number of active sodium channels at the cell membrane, the βENaC or γENaC subunit gene contains a mutation that disrupts the binding site for the Nedd4 (neuronal precursor cell expressed developmentally down-regulated gene 4) family of ubiquitin-protein ligases. (biochemj.org)
  • We confirm that ENaC is associated with the μ2 subunit of the AP-2 (adaptor protein 2) clathrin adaptor. (biochemj.org)
  • A nonhuman transgenic mammal is described whose genome comprises a promoter construct operably linked to a heterologous DNA encoding an epithelial sodium channel β subunit, wherein said promoter construct directs expression of the epithelial sodium channel β subunit in lung epithelial cells of said. (google.com)
  • A nonhuman transgenic mammal is described whose genome comprises a promoter construct operably linked to a heterologous DNA encoding an epithelial sodium channel β subunit, wherein said promoter construct directs expression of the epithelial sodium channel β subunit in lung epithelial cells of said animal, and wherein said transgenic mammal has increased lung mucus retention as compared to the corresponding wild-type mammal. (google.com)
  • When tracing the alpha, beta, and gamma subunits of ENaC back, the team found that the beta subunit appeared slightly before the emergence of Metazoans (multicellular animals with differentiated tissues) roughly 750 million years ago. (phys.org)
  • The appearance of the beta subunit is particularly significant because it is required for the function of the sodium pump. (phys.org)
  • The effect of an acute intravenous volume load, with isotonic and hypertonic saline and glucose, on urinary excretion of AQP2 (u-AQP2), urinary excretion of ENaC gamma subunit fractions (u-ENaCγ) and its relationship to vasopressin (AVP) and kidney function in healthy humans has not been studied by simultaneous measurement of other important regulatory hormones of water and sodium homeostasis such as the renin-angiotensin-aldosterone system (RAAS). (biomedcentral.com)
  • Hence, channel subunit diversity in a single animal is likely to represent diversity in activating stimuli and/or complex channel regulation. (g3journal.org)
  • The scientific team working through the complex interchange found that in the capillaries of the lung, an important subunit of ENaC - called ENaC-alpha - is important as well to strengthening the barrier function of the blood vessels. (eurekalert.org)
  • As the infection generates a strong inflammatory response with some lung edema, we tested if it could modulate the expression of genes involved in lung liquid clearance, such as the α, β and γ subunits of the epithelial sodium channel (ENaC) and the catalytic subunit of Na + -K + -ATPase. (biomedcentral.com)
  • No modulation of α 1 Na + -K + -ATPase mRNA, the catalytic subunit of the sodium pump, was recorded. (biomedcentral.com)
  • These results show that Pseudomonas infection, by modulating ENaC subunit expression, could influence edema formation and clearance in infected lungs. (biomedcentral.com)
  • Most mutations in the SCNN1A gene result in a shortened alpha subunit protein of the ENaC channel. (nih.gov)
  • DOT1L, MLLT3, SIRT1, and SGK1 encode genes in a pathway that controls methylation of the histone H3 globular domain at lysine 79 (H3K79), thereby modulating expression of the ENaCα subunit. (ufl.edu)
  • [7] These cells express Na + and Cl − ion channels, ENaC and CFTR (see Fig. 6 and Fig. 7 in reference [7] ). (wikipedia.org)
  • That Rab plays a role in endocytic recycling, regulating apical recycling of several transmembrane proteins including cystic fibrosis transmembrane conductance regulator/CFTR, epithelial sodium channel/ENaC, potassium voltage-gated channel, and voltage-dependent L-type calcium channel. (uniprot.org)
  • While low levels of CFTR mRNA could be identified in the normal human neutrophil, we were unable to detect CFTR protein in human neutrophil lysates or immunoprecipitates. (ersjournals.com)
  • While mRNA encoding CFTR has been reported to be present at low copy number from preparations of human neutrophils 12 , it is unclear whether this message originates from the neutrophils themselves or from other cells, such as monocytes or lymphocytes present in small but significant numbers in conventional neutrophil isolates. (ersjournals.com)
  • Cystic fibrosis is caused by a mutation in the gene that encodes a protein called cystic fibrosis transmembrane conductance regulator (CFTR), which functions as a chloride channel at the surface of airways and moves chloride out of the cells. (medicalnewstoday.com)
  • CFTR also regulates another protein called epithelial sodium channel (ENaC), which is responsible for transporting sodium into cells. (medicalnewstoday.com)
  • Thus far, scientists have been able to establish that when the CFTR mutation is present, ENaC becomes overactive and causes the cells in the lungs to absorb too much sodium. (medicalnewstoday.com)
  • To observe how CFTR regulates ENaC, Dr. Gentzsch and her team took cells from healthy lung tissue and CF lung tissue and maintained them in a liquid medium. (medicalnewstoday.com)
  • First, what role does CFTR play in regulating ENaC cleavage? (medicalnewstoday.com)
  • CFTR binds to ENaC, so our initial thought was that close contact of ENaC to CFTR protects ENaC from being cleaved. (medicalnewstoday.com)
  • But another possibility is that CFTR is responsible for suppressing ENaC cleavage and activation," said Dr. Gentzsch. (medicalnewstoday.com)
  • In other words, the absence of a normally functioning CFTR protein may cause ENaC overactivity. (medicalnewstoday.com)
  • Because there is more cleavage when the CFTR mutation is present, it implies that healthy CFTR prevents ENaC cleavage and activation, but defective CFTR does not. (medicalnewstoday.com)
  • Either way, Dr. Gentzsch feels that both CFTR and ENaC should be considered when developing therapies for CF. "Successful treatments should address both decreased CFTR function and increased salt absorption caused by ENaC overactivity. (medicalnewstoday.com)
  • Investigation of human airway epithelial cells in vitro provides useful information about the interactions between CFTR and other ion channels as well as the inflammatory response to infection. (physiology.org)
  • CFTR normally acts as a cyclic adenosine monophosphate‐activated chloride channel and as a regulator of other ion channels. (els.net)
  • 3 In the 1990s the putative gene (the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene) was cloned 4 and the affected protein was identified as a gated chloride channel, 5 supporting the hypothesis that CF is linked to abnormal transepithelial ion transport. (bmj.com)
  • 7 In the absence of CFTR, sodium absorption (through the epithelial sodium channel (ENaC)) is upregulated. (bmj.com)
  • We discovered that a specific kind of sweating is rate-limited by CFTR--the anion channel product of the CF gene. (stanford.edu)
  • It has recently been proposed that the initiating event in CF lung disease is depletion of the PCL due to abnormal ion channel activity (i.e. a lack of CFTR), which causes dehydrated mucus to adhere to airway surfaces, preventing it from being cleared (Fig. 2), causing increased bacterial infections. (unc.edu)
  • CFTR is a cAMP-regulated Cl-channel involved in various regulatory processes. (diva-portal.org)
  • Salt and water transport depend on CFTR and the epithelial sodium channel (ENaC), operating in concert with the paracellular pathway through the tight junctions (TJ). (diva-portal.org)
  • Assessment of epithelial sodium channel variants in nonwhite cystic fibrosis patients with non-diagnostic CFTR genotypes. (cdc.gov)
  • The epithelial sodium channel (ENaC) is typically expressed in sodium-absorbing epithelia. (sigmaaldrich.com)
  • Sodium entry via ENaC is the rate-limiting step for transepithelial sodium absorption in various epithelia. (arvojournals.org)
  • Nonvoltage-gated, amiloride-sensitive, sodium channels control fluid and electrolyte transport across epithelia in many organs. (genecards.org)
  • S. Sariban-Sohraby , Role of G-Proteins in the Regulation of Apical Membrane Sodium Permeability by Aldosterone in Epithelia. (elsevier.com)
  • H. O'Brodovich, B. Rafii, A.K. Tanswell, and O. Pitkänen , Induction of Epithelial Sodium Channel Expression and Sodium Transport in Distal Lung Epithelia by Oxygen. (elsevier.com)
  • Members of the ENaC/DEG family are widely expressed in epithelia including kidney ( 14 - 16 ), lung ( 17 ) and colon ( 18 , 19 ). (jcancer.org)
  • Molecular analysis has revealed that the amiloride-sensitive epithelial sodium channel (ENaC), is dysregulated in these disease states, leading to abnormal Na+ reabsorption across body epithelia. (acp.edu)
  • ENaC, the sodium-selective amiloride-sensitive epithelial channel, mediates electrogenic sodium re-absorption in tight epithelia and is deeply associated with human hypertension. (cheric.org)
  • The regulation of the open probability of the epithelial Na + channel (ENaC) by the extracellular concentration of Na + , a phenomenon called "Na + self inhibition," has been well described in several natural tight epithelia, but its molecular mechanism is not known. (rupress.org)
  • 2 In patients with CF the magnitude of sodium absorption across airway epithelia and the response to the sodium channel blocker amiloride are substantially increased compared with normal subjects, coupled with an inability to secrete chloride ions. (bmj.com)
  • In distal epithelia, significant increases in proteolytic cleavage products of alpha-epithelial Na(+) channel (ENaC) and gamma-ENaC were observed, suggesting enhanced tubular sodium reabsorption. (uzh.ch)
  • N. Farman, S. Djelidi, M. Brouard, B. Escoubet, M. Blot-Chabaud, and J.P. Bonvalet , Cell-Specific Expression of EnaC and its Regulation by Aldosterone and Vasopressin in Kidney and Colon. (elsevier.com)
  • In vitro studies with recombinant human enzymes showed LCI699 to be a potent, reversible, competitive inhibitor of aldosterone synthase ( K i = 1.4 ± 0.2 nmol/L in humans) with relative selectivity over 11β-hydroxylase. (biomedcentral.com)
  • Hormonal effects of orally administered LCI699 were examined in rat and monkey in vivo models of adrenocorticotropic hormone (ACTH) and angiotensin-II-stimulated aldosterone release, and were compared with the mineralocorticoid receptor antagonist eplerenone in a randomized, placebo-controlled study conducted in 99 healthy human subjects. (biomedcentral.com)
  • The effects of LCI699 and eplerenone on cardiac and renal sequelae of aldosterone excess were investigated in a double-transgenic rat (dTG rat) model overexpressing human renin and angiotensinogen. (biomedcentral.com)
  • Rat and monkey in vivo models of stimulated aldosterone release predicted human dose- and exposure-response relationships, but overestimated the selectivity of LCI699 in humans. (biomedcentral.com)
  • These results provide new insights into the cardiac and renal effects of inhibiting aldosterone synthase in experimental models and translation of the hormonal effects to humans. (biomedcentral.com)
  • 1. any of the group of corticosteroids, principally aldosterone, primarily involved in the regulation of electrolyte and water balance through their effect on ion transport in epithelial cells of the renal tubules, resulting in retention of sodium and loss of potassium. (thefreedictionary.com)
  • Aldosterone, the most potent mineralocorticoid with regard to electrolyte balance, acts on the distal tubules of the kidneys to enhance the reabsorption of sodium into the plasma. (thefreedictionary.com)
  • Expression of ENaC in kidneys was under aldosterone influence ( Garty , 2000 ). (peerj.com)
  • Pseudohypoaldosteronism (PHA) type I is a rare salt wasting syndrome caused by aldosterone resistance with two distinct forms: an autosomal dominant type, caused by a mutation of the mineralocorticoid receptor with sodium wasting in the kidney, and an autosomal recessive form, resulting from mutations in one of the 3 subunits (alpha, beta, or gamma) of the epithelial Na + channel (ENaC) [ 1 , 2 ]. (hindawi.com)
  • Dr. Rossier will discuss the team's findings at the 7th International Symposium on Aldosterone and the ENaC/Degenerin Family of Ion Channels , sponsored by the American Physiological Society . (phys.org)
  • In humans, the hormone aldosterone affects fluid balance by controlling the epithelial sodium channel (ENaC), a protein that traverses a cell's membrane and facilitates the movement of salt into and out of the cell. (phys.org)
  • This technique has yielded an extraordinary view of the cellular intricacies of CF, which Martina Gentzsch, assistant professor of cell and developmental biology, discussed at the 7th International Symposium on Aldosterone and the ENaC/Degenerin Family of Ion Channels, being held September 18-22 in Pacific Grove, Calif. The meeting is sponsored by the American Physiological Society. (medicalnewstoday.com)
  • Aldosterone is a steroid hormone produced by the adrenal cortex in the adrenal gland to regulate sodium and potassium balance in the blood. (hmdb.ca)
  • Aldosterone increases the permeability of the apical (luminal) membrane of the kidney's collecting ducts to potassium and sodium and activates their basolateral Na+/K+ pumps, stimulating ATP hydrolysis, reabsorbing sodium (Na+) ions and water into the blood, and excreting potassium (K+) ions into the urine. (hmdb.ca)
  • It is used for the treatment of potassium depletion and hypertension, and is the specific therapy for hypertension due to overactivity of the ENaC (Liddle syndrome and several additional genetic causes of the Liddle phenotype - low renin and low aldosterone). (scielo.org.za)
  • For determination of the role of renal MR in aldosterone-driven ENaC-mediated sodium reabsorption, mice with principal cell MR deficiency were generated using the Cre-loxP system. (asnjournals.org)
  • Under standard diet, MR AQP2Cre mice develop normally and exhibit unaltered renal sodium excretion but show strongly elevated aldosterone levels. (asnjournals.org)
  • One important regulator of sodium reabsorption is the mineralocorticoid hormone aldosterone, which activates the transcription factor mineralocorticoid receptor (MR) in its target cells ( 3 ). (asnjournals.org)
  • Sodium reabsorption in the aldosterone-responsive distal tubular segments ( Figure 1A ) is mediated by the amiloride-sensitive epithelial sodium channel (ENaC) that is present in the principal cells of the collecting duct (CD) and connecting tubule (CNT), together with the thiazide-sensitive sodium-chloride co-transporter (TSC) in the distal convoluted tubule (DCT). (asnjournals.org)
  • Aldosterone-regulated ENaC activity is also found in epithelial cells of the distal colon and the ducts of the salivary and sweat glands ( 8 ). (asnjournals.org)
  • We hypothesized that aldosterone regulates the expression of miRNAs in the early phase of induction to control the expression of target genes that stimulate ENaC activity. (nih.gov)
  • Our findings implicate miR-466g as a novel early-phase aldosterone responsive miRNA that regulates SGK1 and ENaC in CCD cells. (nih.gov)
  • Renin-aldosterone response, urinary Na/K ratio and growth in pseudohypoaldosteronism patients with mutations in epithelial sodium channel (ENaC) su. (growkudos.com)
  • Aldosterone is the primary of several endogenous members of the class of mineralocorticoids in human. (answers.com)
  • citation needed] Aldosterone is responsible for the reabsorption of about 2% of filtered sodium in the kidneys, which is nearly equal to the entire sodium content in human blood under normal GFR (glomerular filtration rate). (answers.com)
  • Join us for the APS Aldosterone and ENaC in Health and Disease: The Kidney and Beyond conference. (the-aps.org)
  • This in-depth, four-day conference is the ninth in a series on the topic of aldosterone and the epithelial sodium channel (ENaC). (the-aps.org)
  • The ASIC3 gene is one of the five paralogous genes that encode proteins that form trimeric acid-sensing ion channels (ASICs) in mammals. (wikipedia.org)
  • This gene encodes a member of the ASIC/ENaC superfamily of proteins. (wikipedia.org)
  • The aims of this study were to investigate effects of testosterone on expression of α , β and γ -epithelial sodium channel (ENaC) proteins and messenger RNAs (mRNAs) in kidneys, the channel known to be involved in Na + reabsorption, which subsequently can affect the blood pressure. (peerj.com)
  • The distribution of α , β and γ -ENaC proteins in kidneys were observed by immunofluorescence. (peerj.com)
  • The α , β and γ -ENaC proteins and mRNA levels in kidneys were enhanced in rats which received testosterone-only treatment. (peerj.com)
  • In these rats, α , β and γ -ENaC proteins were distributed in the distal tubules and collecting ducts of the nephrons. (peerj.com)
  • Co-treatment with flutamide or finasteride resulted in the levels of α , β and γ -ENaC proteins and mRNAs in kidneys to decrease. (peerj.com)
  • ENaCs are heterotrimeric proteins that form channels in the cell membrane and allow the passage of sodium ions (Na+). (phys.org)
  • As neutrophilic inflammation including increased release of human neutrophil elastase (HNE) is a salient feature of AECOPD, we hypothesized that HNE impairs airway epithelial defense against NTHi by degrading airway epithelial host defense proteins such as short palate, lung, and nasal epithelium clone 1 (SPLUNC1). (jove.com)
  • Transfected RNA and proteins were both expressed in low abundance, similar to the endogenous levels of ENaC in native cells. (semanticscholar.org)
  • Since mono- or multi-ubiquitination of other membrane proteins is a signal for their internalization by clathrin-mediated endocytosis and subsequent trafficking, our results support a model whereby ubiquitin and clathrin adaptor binding sites act in concert to remove ENaC from the cell surface. (biochemj.org)
  • To evaluate the role of these proteins in regulating amiloride-sensitive sodium channel activity, multiple Rab isoforrns 3, 5, 6, and Rab27a were expressed in HT-29 cells. (cheric.org)
  • Biotinylation studies revealed that modulation of ENaC function is due to the reduced apical expression of channel proteins. (cheric.org)
  • These observations point to the involvement of multiple Rab proteins in ENaC transport through intracellular routes like exocytosis, recycling from ER to plasma membrane or degradation and thus serve as potential target for human hypertension. (cheric.org)
  • Bachmann S, Bostanjoglo M, Schmitt R, Ellison DH (1999) Sodium transport-related proteins in the mammalian distal nephron-distribution, ontogeny and functional aspects. (springer.com)
  • We report here that 14-3-3 proteins participate in this regulatory process through a direct interaction with a phosphorylated form of human Nedd4-2 (a human gene product of KIAA0439, termed hNedd4-2). (proteopedia.org)
  • Our findings suggest that 14-3-3 proteins modulate the cell surface density of ENaC cooperatively with Sgk1 kinase by maintaining hNedd4-2 in an inactive phosphorylated state. (proteopedia.org)
  • 14-3-3 proteins modulate the expression of epithelial Na+ channels by phosphorylation-dependent interaction with Nedd4-2 ubiquitin ligase. (proteopedia.org)
  • Ichimura T, Yamamura H, Sasamoto K, Tominaga Y, Taoka M, Kakiuchi K, Shinkawa T, Takahashi N, Shimada S, Isobe T. 14-3-3 proteins modulate the expression of epithelial Na+ channels by phosphorylation-dependent interaction with Nedd4-2 ubiquitin ligase. (proteopedia.org)
  • Using the epithelial sodium channel (ENaC), essential for kidney control of blood pressure, we have shown that ubiquitin pathway proteins control the number of ENaCs at the cell surface resulting in changes in Na+ absorption. (otago.ac.nz)
  • As part of a protein interaction screen we discovered that COMMD family proteins also regulate ENaC trafficking. (otago.ac.nz)
  • CLC proteins form a gene family that comprises nine members in mammals, at least four of which are involved in human genetic diseases. (hmdb.ca)
  • Control of sodium reabsorption in kidney is essential for maintaining sodium balance and requires tight regulation of the activity of several transport proteins, which are differentially expressed in distinct functional segments of the renal tubules ( 1 , 2 ). (asnjournals.org)
  • Degenerin/epithelial sodium channels (DEG/ENaC) represent a large family of animal-specific membrane proteins. (g3journal.org)
  • Subcellular localization of human Chr21 proteins may contribute to further understanding of the functions and regulatory mechanisms of the genes that code for these proteins. (biomedcentral.com)
  • The results from this study reveal novel functional features of human Chr21 proteins, which should contribute to further understanding of the molecular pathology of Down's syndrome. (biomedcentral.com)
  • We optimized this platform for high-throughput protein co-localization studies and applied it to the characterization of human chromosome 21 (Chr21) encoded proteins. (biomedcentral.com)
  • At the protein level, β- and γ-ENaC subunits showed distinct distribution patterns and could be immunolocalized primarily to the cell membranes of epithelial cells of the cornea and to the conjunctiva, iris, ciliary body, lens, and retinal pigment epithelium but also to vascular endothelial cells, smooth muscle cells, stromal cells, and retinal neurons. (sigmaaldrich.com)
  • As a result of the mutations, the protein is not degraded, and more ENaC channels remain at the cell surface. (medlineplus.gov)
  • Acid-sensing ion channel 3 (ASIC3) also known as amiloride-sensitive cation channel 3 (ACCN3) or testis sodium channel 1 (TNaC1) is a protein that in humans is encoded by the ASIC3 gene. (wikipedia.org)
  • In type III cells, sour taste is initiated when protons enter through apically located proton-selective ion channels: polycystic kidney disease 2-like 1 protein (PKD2L1) and polycystic kidney disease 1-like 3 protein (PKD1L3) channels. (genome.jp)
  • A research team has developed the first small molecule that can reversibly activate a key protein involved in balancing sodium levels, paving the way for drugs that can treat low blood pressure and related conditions. (eurekalert.org)
  • Following sacrifice, the kidneys were removed and were subjected for α , β and γ -ENaC protein and mRNA expression analyses by Western blotting and Real-time PCR (qPCR) respectively. (peerj.com)
  • In conclusions, increases in α , β and γ -ENaC protein and mRNA levels in kidneys mainly in the distal tubules and collecting ducts under testosterone influence might lead to enhance Na + reabsorption which subsequently might cause an increase in blood pressure. (peerj.com)
  • A6 model renal epithelial cells were stably transfected with enhanced green fluorescent protein (EGFP)-tagged alpha- or beta-subunits of the epithelial Na(+) channel (ENaC). (semanticscholar.org)
  • The immunoprecipitation experiments suggest protein-protein interaction of Rab3 and Rab27a with epithelial sodium channel. (cheric.org)
  • 12. The method of claim 1 , wherein said promoter is selected from the group consisting of the CCSP promoter, the surfactant protein C promoter, the cytokeratin 18 promoter, and the human forkhead homologue 4 promoter. (google.com)
  • GSK2225745, was identified as a potent inhibitor of ENaCα mRNA (EC(50) (half maximal effective concentration) = 0.4 nmol/l, maximum knockdown = 85%) and protein levels in A549 cells. (cfgenetherapy.org.uk)
  • NED4L_HUMAN ] E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. (proteopedia.org)
  • The ubiquitin E3 protein ligase Nedd4-2 is a physiological regulator of the epithelial sodium channel ENaC, which is essential for transepithelial Na+ transport and is linked to Liddle's syndrome, an autosomal dominant disorder of human salt-sensitive hypertension. (proteopedia.org)
  • Nedd4-2 function is negatively regulated by phosphorylation via a serum- and glucocorticoid-inducible protein kinase (Sgk1), which serves as a mechanism to inhibit the ubiquitination-dependent degradation of ENaC. (proteopedia.org)
  • The human kallikrein (KLK1) protein plays a vital role in normal kidney function. (yahoo.com)
  • Then the team studied proteolytic cleavage of ENaC, a process in which the ENaC protein is cut by enzymes called proteases at specific sites on the protein. (medicalnewstoday.com)
  • Immunofluorescence showed that canine chondrocytes expressed ENaC protein. (ovid.com)
  • Therefore, determination of the subcellular protein distribution would provide an important insight into the function of human Chr21 genes. (biomedcentral.com)
  • Comparison of paracrine soluble factors in MSC media showed that the IL-1 receptor antagonist and prostaglandin E2 were markedly increased while keratinocyte growth factor (KGF) was twofold lower in HCYT-MSC-M compared with MSC-M. In AECs, hypoxia plus cytomix increased protein permeability, reduced amiloride-sensitive short-circuit current (AS-Isc), and also decreased the number of α-epithelial sodium channel (α-ENaC) subunits in the apical membrane. (nih.gov)
  • the effects of high sodium on eNOS phosphorylation and NO production were inhibited by a specific ENaC blocker, amiloride. (emory.edu)
  • In vitro potency, maximal efficacy, rate of recovery from maximal block of ENaC, and rate of drug absorption were compared for amiloride, benzamil, and phenamil in cultured human and ovine bronchial epithelial cells. (aspetjournals.org)
  • Amiloride, "a potassium-sparing diuretic", is a relatively selective ENaC blocker. (aspetjournals.org)
  • The proposed mechanism of amiloride action is an open channel block in the exofacial domain of ENaC ( Horisberger, 1998 ). (aspetjournals.org)
  • Hirsh, 2002 ) and rapid reversal from ENaC block ( Hirsh, 2002 ) also limited the clinical utility of amiloride. (aspetjournals.org)
  • Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. (genecards.org)
  • J.A. Schafer, L. Li, D. Sun, R.G. Morris, and T.W. Wilborn , Regulation of Amiloride-Sensitive Na+ Channels in the Renal Collecting Duct. (elsevier.com)
  • P.R. Smith , cAMP Mediated Regulation of Amiloride-Sensitive Sodium Channels: Channel Activation or Channel Recruitment? (elsevier.com)
  • S.C. Kinnamon, B. Lindemann, and T.A. Gilbertson , Amiloride Sensitive Sodium Channels in Taste. (elsevier.com)
  • The members of this family are amiloride-sensitive sodium channels that contain intracellular N and C termini, 2 hydrophobic transmembrane (TM) regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. (wikipedia.org)
  • Here, we show that treating Xenopus laevis oocytes expressing ENaC and PPARγ with the TZD rosiglitazone (RGZ) produced a twofold increase of amiloride-sensitive sodium current (Iam), as measured by two-electrode voltage clamp. (deepdyve.com)
  • The human SCNN1A, B and G genes encode the heteromeric ENaC channel, a constitutively active, amiloride-sensitive Na+-selective ion channel. (criver.com)
  • While previous studies have examined the role of amiloride in low-renin hypertension, and as an additional agent the conventional treatment of hypertension, no human trials have tested whether ENaC inhibitors impact blood pressure and volume status in the setting of proteinuria. (clinicaltrials.gov)
  • Amiloride-sensitive cation channel 1, neuronal (degenerin) , also known as ACCN1 , is a human gene . (wikidoc.org)
  • Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF) patients. (sigmaaldrich.com)
  • However, the dose of amiloride is limited by the mechanism-based side effect of hyperkalaemia resulting from renal ENaC blockade. (sigmaaldrich.com)
  • The in vitro potency and duration of action of NVP-QBE170 were compared with amiloride and a newer ENaC blocker, P552-02, in primary human bronchial epithelial cells (HBECs) by short-circuit current. (sigmaaldrich.com)
  • In vivo, intratracheal (i.t.) instillation of NVP-QBE170 attenuated ENaC activity in the guinea pig airways with greater potency and duration of action than that of amiloride without inducing hyperkalaemia in either guinea pig or rat. (sigmaaldrich.com)
  • One of the best known potassium sparing diuretics - amiloride - blocks the action of so-called epithelial sodium channels (ENaCs), which have diverse physiological functions. (phys.org)
  • This provides the first optical tool for an amiloride-sensitive ion channel . (phys.org)
  • ASICs are gated by protons and belong to the family of degenerin/epithelial sodium channels (DEG/ENaC), a large group of ion channels that are sensitive to the diuretic amiloride ( Kellenberger and Schild, 2002 ). (embopress.org)
  • Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. (abcam.com)
  • Rab3 and Rab27a inhibited ENaC currents, while the expression of other Rab isoforms failed to elicit any statistically significant effect on amiloride-sensitive currents. (cheric.org)
  • In human nasal epithelial cells, GSK2225745 also produced potent and long-lasting (≥72 hours) suppression of ENaCα mRNA levels which was associated with significant inhibition of ENaC function (69% inhibition of amiloride-sensitive current in cells treated with GSK2225745 at 10 nmol/l). (cfgenetherapy.org.uk)
  • Amiloride is an antagonist of the renal tubular epithelial sodium channel (ENaC). (scielo.org.za)
  • Amiloride is a potassium-sparing diuretic that blocks the epithelial sodium channel (ENaC) in the collecting duct of the kidney, resulting in natriuresis and retention of potassium and magnesium. (scielo.org.za)
  • [1] and (ii) if half the dose is used to minimise electrolyte abnormalities, the dose of amiloride (2.5 mg) is insufficient to adequately target the ENaC. (scielo.org.za)
  • Mammalian amiloride-sensitive epithelial Na+ channel (ENaC) can be composed by different combinations of four homologous subunits, α, β, γ and δ. (tcd.ie)
  • Amiloride-sensitive epithelial Na channel current of similar size was present in both cell types while forskolin-activated CF transmembrane conductance regulator current was lacking in CF cells. (physiology.org)
  • Amiloride, a direct ENaC blocker, but not spironolactone, prevented protracted fluid retention in these patients. (asnjournals.org)
  • Although the physiological functions of most family members are not known, some have been shown to act as nonvoltage gated, amiloride-sensitive sodium channels. (g3journal.org)
  • Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors. (semanticscholar.org)
  • Interestingly, KGF-deprived MSC-M were unable to restore amiloride-sensitive sodium transport, indicating a possible role for KGF in the beneficial effect of MSC-M. These results indicate that MSC-M may be a preferable therapeutic option for ALI. (nih.gov)
  • The TNFalpha receptor TNFRSF1A and genes encoding the amiloride-sensitive sodium channel ENaC as modulators in cystic fibrosis. (cdc.gov)
  • Previous studies have shown that PPARγ activation by TZD enhances the expression or function of the epithelial sodium channel (ENaC) through different mechanisms. (deepdyve.com)
  • The function of the epithelial sodium channel, or ENaC, which helps move fluid out of air sacs normally, is even more in demand in the face of pneumonia, but the toxin impairs its ability in both the air sacs and capillaries, the scientists have now shown. (eurekalert.org)
  • Gene Ontology (GO) annotations related to this gene include WW domain binding and ligand-gated sodium channel activity . (genecards.org)
  • The channel is composed of alpha, beta, and gamma subunits, each of which is produced from a different gene. (medlineplus.gov)
  • It is thought that a mutation or gene variation in the SCNN1G gene can disrupt sodium transport and fluid balance, which leads to the signs and symptoms of cystic fibrosis-like syndrome. (medlineplus.gov)
  • Human ASIC3 genome location and ASIC3 gene details page in the UCSC Genome Browser. (wikipedia.org)
  • In humans, it is encoded by the BPIFA1 (Bactericidal/permeability-increasing fold-containing family A1) gene, previously called PLUNC. (wikipedia.org)
  • This gene is the human homolog of murine plunc, and like the mouse gene, is specifically expressed in the airways and nasopharyngeal regions. (wikipedia.org)
  • This gene encodes a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. (wikidoc.org)
  • Mutation of ENaC gene could lead to hypotension, while its prolonged activation could lead to severe hypertension ( Bubien , 2010 ). (peerj.com)
  • She was found to have a known mutation in the SCNN1A gene and subsequently required treatment with sodium supplementation. (hindawi.com)
  • Bio-Rad collaborated with Biogazelle, leaders in real-time PCR research, to design and experimentally validate PCR primers for gene expression assays across the human and mouse transcriptomes. (bio-rad.com)
  • Either way, the fact that ENaC gene family appeared just before the emergence of Metazoans suggests it is somehow linked to the development of multi-celled organisms, he said. (phys.org)
  • Renal nursing a practical approach chapter onechapter twoinitiation and maintenance of cell turnover in human disease gene pax which marks the area surrounding the ureteric bud branching h e wild type by e ureteric bud. (nationalnewstoday.com)
  • SCNN1, an epithelial cell sodium channel gene in the conserved linkage group onmouse chromosome 6 and human chromosome 12.Genomics. (tcdb.org)
  • SCNN1, a gene encoding a nonvoltage-gated sodium channel, was detected using a rat colon cDNA probe with homology to Caenorhabditis elegans degenerin genes. (tcdb.org)
  • Cystic fibrosis (CF) is caused by alterations in the CF transmembrane conductance regulator (CFTCR) gene that result in deranged sodium and chloride ion transport channels. (hmdb.ca)
  • Germline inactivation of the mineralocorticoid receptor (MR) gene in mice results in postnatal lethality as a result of massive loss of sodium and water. (asnjournals.org)
  • The regulatory elements of the mouse AQP2 gene were used to drive Cre recombinase expression in ENaC-expressing principal cells of the connecting tubule (CNT) and collecting duct (CD). (asnjournals.org)
  • The candidate gene approach to understand the genetics of human essential hypertension identified two important genes contributing in the regulation of blood pressure, the genes that encode for angiotensinogen ( 17 ) and the epithelial sodium channel (ENaC). (aaccjnls.org)
  • SCNN1A gene mutations lead to reduced or absent ENaC channel activity. (nih.gov)
  • Genetic analysis of Rwandan patients with cystic fibrosis-like symptoms: identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants. (cdc.gov)
  • any of a group of hormones elaborated by the cortex of the adrenal gland , so called because of their effects on sodium, chloride, and potassium concentrations in the extracellular fluid. (thefreedictionary.com)
  • XVIII (1928) The use of sodium chloride, potassium chloride, sodium bromide, and potassium bromide in cases of arterial hypertension which are amenable to potassium chloride. (springer.com)
  • GABA(A) receptors are pentameric complexes that function as ligand-gated chloride ion channels. (hmdb.ca)
  • Channels that also contribute to the balance of salt and water across the apical membrane include calcium‐activated chloride channel ( CaCC ) and epithelial sodium channel ( ENaC ). (els.net)
  • This can be assessed in the airway in vivo by measuring potential difference (PD)-that is, the voltage generated across an electrically tight epithelium by the active transport of charged sodium and chloride ions. (bmj.com)
  • This question is important, since potential therapeutic strategies currently target both loops of the cascade, for example, with sodium channel blockers and chloride secretagogues. (bmj.com)
  • This has been explained by chloride secretion through alternative channels in the airway. (bmj.com)
  • Its mainly works to control reabsorption of sodium and chloride and secretion of potassium and hydrogen. (answers.com)
  • ENaC is a heteromeric channel made of three subunits (α, β and γ) encoded by 3 different genes SCNN1a, SCNN1b and SCNN1g, respectively. (intechopen.com)
  • The genes encoding the epithelial Na + channel/degenerin (ENaC/DEG) were firstly discovered in the early 1990s. (jcancer.org)
  • By searching for genes that descended from a common ancestral DNA sequence (homologs), the researchers found that the emergence of ENaC and Na, K-ATPase (sodium pump), an enzyme that also plays a role in sodium transport, coincided with the emergence of multi-celled organisms. (phys.org)
  • Dr. Rossier said that although it is possible that the genes for ENaC originated in the common ancestor of eukaryotes and were lost in all branches except the Metazoa and the Excavates, there is another possibility. (phys.org)
  • Whether a Metazoan transferred the genes for ENaC to N. gruberi or the other way around, Dr. Rossier is not sure. (phys.org)
  • We also identified representative genes from five of the six DEG/ENaC subfamilies in a mosquito genome, suggesting that the core DEG/ENaC subfamilies were already present early in the dipteran radiation. (g3journal.org)
  • Mutations in the Scnn1b and Scnn1g genes, which encode the β and the γ subunits of ENaC, cause a severe form of hypertension (Liddle syndrome). (aaccjnls.org)
  • In lungs, ENaC regulates mucus secretion and aids in the protection of the airway surface ( Randell and Boucher, 2006 ). (intechopen.com)
  • Specifically it regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. (hmdb.ca)
  • Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. (genecards.org)
  • In the kidney, ENaC channels open in response to signals that sodium levels in the blood are too low, which allows sodium to flow into cells. (medlineplus.gov)
  • From the kidney cells, this sodium is returned to the bloodstream (a process called reabsorption) rather than being removed from the body in urine. (medlineplus.gov)
  • ENaC expressed in kidney and colon is a therapeutic target in hypertension, congestive heart disease and inflammatory bowel disease. (criver.com)
  • 2004 ). There were evidences which suggest the involvement of testosterone in regulating kidney ENaC expression. (peerj.com)
  • Quan and colleagues ( 2004 ) reported that dihydrotestosterone (DHT) injection to adult male Sprague-Dawley rats could increase Na + reabsorption in kidney proximal tubules, suggesting that this could be mediated via ENaC. (peerj.com)
  • 2005 ) reported that sub-chronic (14 days) treatment of adult male Wistar rats with testosterone resulted in elevated α - Enac mRNA levels in kidney homogenates. (peerj.com)
  • In the kidney, the so-called alpha/beta/gamma subtype is involved in the resorption of sodium from the urine, which reduces water loss and maintains blood volume. (phys.org)
  • The researchers have shown that the novel photoamiloride functions in this way on ENaCs in amphibian cells as well as in human embryonal kidney cells and in a tissue-culture model of human lung epithelium. (phys.org)
  • In the autosomal recessive form, also known as systemic PHA type I, patients have multisystem disease with sodium wasting in the kidney, lungs, colon, sweat, and salivary glands. (hindawi.com)
  • The cited work of the authors was supported by a collaborative project grant from the Zurich Center for Integrative Human Physiology (ZIHP), by research funds from the Swiss National Centre for Competence in Research "Kidney.CH," and by a project grant (310030_143929/1) from the Swiss National Science Foundation. (springer.com)
  • 11 The ENaC is the final regulator of sodium balance in the kidney and therefore plays a crucial role in sodium regulation and blood pressure (BP) control. (scielo.org.za)
  • The knockout mice show impaired epithelial sodium channel (ENaC) activity in kidney and colon. (asnjournals.org)
  • Immunohistochemistry-Paraffin: epithelial Sodium Channel gamma Antibody (5c2) [NBP2-41374] - Staining of Human kidney tissue. (novusbio.com)
  • We constructed an SGK1 3'-untranslated region luciferase reporter and found that cotransfection of miR-466g suppressed luciferase activity in human embryonic kidney-293 cells in a dose-dependent manner. (nih.gov)
  • Antibody is specific for the neoepitope generated after proteolytic cleavage of human gENaC and recognizes the C-terminal fragment starting from amino acid residue 182. (novusbio.com)
  • Enhanced proteolytic cleavage of ENaC points to a novel mechanism of channel activation which may involve the action of filtered plasma proteases. (uzh.ch)
  • Background and objectives Thiazolidinediones (pioglitazone and rosiglitazone) induce renal epithelial sodium channel (ENaC)-mediated sodium reabsorption, resulting in plasma volume (PV) expansion. (asnjournals.org)
  • The renal epithelial sodium channel (ENaC) provides a mechanism for fine-tuning sodium excretion, and is a major regulator of blood pressure homeostasis. (ufl.edu)
  • In addition to regulating the amount of sodium in the body, the flow of sodium ions helps control the movement of water in tissues. (medlineplus.gov)
  • The pore of the channel through which ions selectively flow from the extracellular side into the cytoplasm is formed by the three TM2 regions of the trimer. (wikipedia.org)
  • Secondary effects are related to the reabsorption of water, serum levels of sodium and potassium, anion reabsorption, and secretion of hydrogen ions. (thefreedictionary.com)
  • a hormone, secreted by the adrenal cortex, that maintains normal blood volume, promotes sodium and water retention, and increases urinary excretion of potassium and hydrogen ions. (thefreedictionary.com)
  • Turning off the light or irradiating the cells with green light alters the shape of the compound in such a way that the block is released and sodium ions flow through the channel pore into the cell. (phys.org)
  • There has been much speculation that aberrant influx of sodium ions through ENaCs might contribute to the pathogenesis of neuronal diseases by causing persistent, uncontrolled firing by nerve cells. (phys.org)
  • In addition, our photoamiloride/ENaC system can be used to manipulate the polarization state of cells - the magnitude of the electrical potential across the cell membrane - by altering the flow of sodium ions through these channels," Dirk Trauner adds. (phys.org)
  • Our data suggest that benzamil inhibits RVI by reducing the influx of Na+ ions through ENaC/Deg-like ion channels and present ENaC/Deg as a possible target for pharmacological modulation of chondrocyte volume. (ovid.com)
  • Reabsorption of sodium into the blood is linked with removal of potassium from the blood, so excess sodium reabsorption leads to hypokalemia. (medlineplus.gov)
  • This condition typically begins in infancy and is characterized by low levels of sodium (hyponatremia) and high levels of potassium (hyperkalemia) in the blood, and severe dehydration due to the loss of excess sodium and fluid in urine. (medlineplus.gov)
  • The primary effects of the mineralocorticoids are increasing the reabsorption of sodium and the secretion of potassium in the renal tubules. (thefreedictionary.com)
  • One of the steroids of the cortex of the suprarenal gland that influence salt (sodium and potassium) metabolism. (thefreedictionary.com)
  • Sodium and potassium normalized within 2 days. (hindawi.com)
  • Bailey MA, Cantone A, Yan Q, MacGregor GG, Leng Q, Amorim JB, Wang T, Hebert SC, Giebisch G, Malnic G (2006) Maxi-K channels contribute to urinary potassium excretion in the ROMK-deficient mouse model of type II Bartter's syndrome and in adaptation to a high-K diet. (springer.com)
  • Moreover, tissue acidosis is well known to be painful ( 13 ) and inhibition of ASICs in healthy human volunteers ( 14 , 15 ) has revealed the important role of these channels in sensing acid-induced pain provoked by cutaneous acidification. (pnas.org)
  • The goal of these planned studies of P-1037 is to determine whether ENaC inhibition can improve lung function in people with CF, including those with mutations unlikely to respond to treatment with the investigational combination of lumacaftor and ivacaftor. (cnbc.com)
  • ENaC inhibition represents a promising opportunity to potentially enhance the benefit of existing treatments for people with CF, and we have worked diligently to bring P-1037 from our research labs and into Phase 2 development," said Paul Boucher, President and Chief Executive Officer of Parion. (cnbc.com)
  • In vivo, topical delivery of GSK2225745 in a lipid nanoparticle formulation to the airways of mice resulted in significant inhibition of the expression of ENaCα in the lungs. (cfgenetherapy.org.uk)
  • We used immunohistochemistry and patch-clamp electrophysiology to investigate ENaC expression and video microscopy to analyse the effects of pharmacological inhibition of ENaC/Deg on cell volume regulation. (ovid.com)
  • We have studied the kinetics of Na + self inhibition on human ENaC expressed in Xenopus oocytes. (rupress.org)
  • Self inhibition could be prevented by exposure to extracellular protease, a treatment known to activate ENaC or by treatment with p- CMB. (rupress.org)
  • These results indicate that Na + self inhibition is an intrinsic property of sodium channels resulting from the expression of the α, β, and γ subunits of human ENaC in Xenopus oocyte. (rupress.org)
  • The (patho-)physiological roles of ENaC in the various localizations in the eye remain to be determined. (sigmaaldrich.com)
  • However, the precise localization and (patho) physiological relevance of ENaC in the eye are still unclear. (arvojournals.org)
  • Further studies will be needed to evaluate ENaC expression patterns under various physiological and pathophysiological conditions and to establish its role for ocular function. (arvojournals.org)
  • The physiological relevance and properties of these human variants have so far never been studied. (pnas.org)
  • The epithelial Na + channel/degenerin (ENaC/DEG) superfamily, including the acid-sensing ion channels (ASICs), is characterized by a high degree of similarity in structure but highly diverse in physiological functions. (jcancer.org)
  • These ion channels have been shown to be important in several physiological functions of normal epithelial cells, including salt homeostasis, fluid transportation and cell mobility. (jcancer.org)
  • In summary, our analyses support a rapid early diversification of the DEG/ENaC family in Diptera followed by physiological and/or cellular specialization. (g3journal.org)
  • Together, these data indicate that DEG/ENaC channels have evolved to serve many different physiological functions, acting as ionotropic receptors to diverse extracellular stimuli. (g3journal.org)
  • Venom toxins in the exploration of molecular, physiological and pathophysiological functions of acid-sensing ion channels. (semanticscholar.org)
  • whole animal physiological studies and human studies and clinical trials of emerging novel MR antagonists and other drugs. (the-aps.org)
  • M. Driscoll, H.A. Thieringer, S. Sahota, and I. Mano , C. elegans Members of the DEG/EnaC Channel Superfamily: Form and Function. (elsevier.com)
  • All four ENaC subunits (αβγδ) are expressed in the normal human eye, with distinct localization of subunits possibly reflecting different functional states of the channel. (sigmaaldrich.com)
  • ENaC is expressed in epithelial and non-epithelial tissues of the human eye with a distinct localization of subunits possibly reflecting different functional states of ENaC. (arvojournals.org)
  • Functional channels have been proposed to result from the trimeric association of subunits ( 4 ), leading to homomeric or heteromeric channels. (pnas.org)
  • In collaboration with other investigators, Dr. Rao's research group characterized the functional role of gamma-subnit in ENaC function and the functional role of ENaC in renal sodium reabsorption. (acp.edu)
  • Without it, a functional sodium pump cannot be expressed at the cell surface. (phys.org)
  • Annexin II light chain p11 interacts with ENaC to increase functional activity at the membrane. (otago.ac.nz)
  • In this study, we investigated whether canine chondrocytes express functional ENaC/Deg-like ion channels and, if so, what their function may be. (ovid.com)
  • The tissue distribution and functional characterization of human VR1. (semanticscholar.org)
  • 9. The method of claim 1 , wherein said test compound is an ENaC regulator. (google.com)
  • Her poster presentation is entitled, "The Cystic Fibrosis Transmembrane Conductance Regulator Inhibits Proteolytic Stimulation of ENaC. (medicalnewstoday.com)
  • These channels are found at the surface of certain cells called epithelial cells in many tissues of the body, including the kidneys, lungs, and sweat glands. (medlineplus.gov)
  • For example, ENaC channels in lung cells help regulate the amount of fluid in the lungs. (medlineplus.gov)
  • The reduced function of ENaC channels in lung epithelial cells leads to excess fluid in the lungs and recurrent lung infections. (medlineplus.gov)
  • Inhaled ENaC blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal hydration and MCC in the lungs of CF patients. (sigmaaldrich.com)
  • The human epithelial sodium channel (ENaC) controls sodium flow across many tissues such as the lungs, kidneys, and colon, and it is vital to maintaining proper salt balance and blood pressure. (eurekalert.org)
  • The sustained yet reversible action of S3969 makes it a good model to build future drugs aimed at improving hypotension, neonatal pulmonary edema (reduced sodium uptake in the lungs can lead to fluid retention), and renal salt wasting disorders. (eurekalert.org)
  • As a result of decreased sodium-dependent liquid absorption in the lungs, children often develop pulmonary symptoms including congestion, wheezing, and recurrent pulmonary infections. (hindawi.com)
  • In humans , for example, motile cilia are found in the lining of the trachea (windpipe), where they sweep mucus and dirt out of the lungs. (rug.nl)
  • Water follows the sodium from the cells' surfaces into the cells, and as a result, the airways become dry and mucous becomes thick and sticky, leading to infections in the lungs. (medicalnewstoday.com)
  • The cells' surfaces were exposed to air, which prompted the cells to grow and behave as though they were still inside human lungs. (medicalnewstoday.com)
  • Sodium channels in the cells that line the tiny capillaries in our lungs play an important role in keeping those capillaries from leaking and potentially worsening conditions like pneumonia, scientists. (eurekalert.org)
  • We also provided more evidence that targeting these channels with the TIP peptide or something similar is a solid strategy for reducing dangerous fluid volume in your lungs," says Lucas. (eurekalert.org)
  • In conclusion, our data support the hypothesis that ENaC blocker aerosol therapy increases MC. (aspetjournals.org)
  • NVP-QBE170: an inhaled blocker of the epithelial sodium channel with a reduced potential to induce hyperkalaemia. (sigmaaldrich.com)
  • 7. The method of claim 1 , wherein said test compound is a sodium channel blocker. (google.com)
  • The increase in channels at the cell surface allows the reabsorption of excess sodium (followed by water), which leads to hypertension. (medlineplus.gov)
  • Another possible explanation is that an ENaC activator, like plasmin, contributes to the generation of incident hypertension in some individuals. (clinicaltrials.gov)
  • Interestingly, while there are available drugs that can block over-active sodium channels, which can help treat hypertension and other disorders, no one has yet found effective ENaC activators. (eurekalert.org)
  • Sodium ion transport is defective in several human disease conditions that include cystic fibrosis (CF), hypertension, Liddle's syndrome and others. (acp.edu)
  • Her lab is interested in elucidating the atomic-scale mechanism of function of epithelial sodium channels (ENaC), how perturbation in the ENaC channel disrupt activity contributing to human diseases like hypertension, and how molecules that directly modulate ENaC activity work. (nih.gov)
  • Mutations increasing WNK1 kinase expression in humans cause the pseudohypoaldosteronism type II hypertension syndrome. (biologists.org)
  • Human glomerulonephritis (GN) is characterized by sustained proteinuria, sodium retention, hypertension, and edema formation. (uzh.ch)
  • It discusses the pivotal role of the renal distal tubule for the regulation of urinary K + and Na + excretion and blood pressure and highlights that it depends on the coordinated interaction of different nephron portions, epithelial cell types, and various ion channels, transporters, and ATPases. (springer.com)
  • The degree of water transport, via aquaporin2 water channels (AQP2), and sodium transport, via epithelial sodium channels (ENaC) in renal collecting duct principal cells are reflected by the level of urinary excretion of AQP2 (u-AQP2) and the γ-fraction of ENaC (u-ENaCγ). (biomedcentral.com)
  • In this present study we wanted to study the sodium and water transport in the distal nephron by measuring 1) the excretion of u-AQP2 and u-ENaCγ 2) associated regulating hormones and 3) the renal response after volume expansion in healthy humans. (biomedcentral.com)
  • The fine regulation of sodium balance in terrestrial vertebrates is realized mostly by a tight control of Na + urinary excretion. (rupress.org)
  • Thus, the regulation of Na + excretion occurs mostly by the control of the density and the open probability of these apical membrane Na + channels. (rupress.org)
  • Increased renal sodium and water excretion, resulting in continuous loss of body weight, occur under low-sodium diet. (asnjournals.org)
  • Several reports suggest that ENaC is also expressed in ocular tissues and may play a role in aqueous humor secretion and glaucoma. (sigmaaldrich.com)
  • In humans , sweating is primarily a means of thermoregulation , which is achieved by the water-rich secretion of the eccrine glands. (wikipedia.org)
  • MSC-M were collected from human MSCs exposed for 12 h to either normoxia (MSC-M) or to hypoxia plus cytomix (HCYT-MSC-M). This latter condition was used to model the effect of alveolar inflammation and hypoxia on paracrine secretion of MSCs in the injured lung. (nih.gov)
  • Renal sodium retention and extracellular fluid volume expansion are hallmarks of nephrotic syndrome. (clinicaltrials.gov)
  • The proteolytic activation of ENaC would generate a primary defect in renal sodium handling, a mechanism that may be a particularly important factor leading to increases in extracellular fluid volume and BP that accompany nephrotic syndrome. (clinicaltrials.gov)
  • Epithelium is the most common component of human tissues, which mainly functions in body protection, regulation of fluid homeostasis and exchange, and sensation of external stimuli ( 1 , 2 ). (jcancer.org)
  • Recent studies have revealed that various epithelial ion channels play an important role in the regulation of fluid/ion homeostasis ( 3 ). (jcancer.org)
  • Several studies have shown that the ENaC/DEG channels are responsible for Na + uptake and fluid transportation ( 20 ) and are necessary to maintain the Na + balance, fluid balance and homeostasis for epithelial cells. (jcancer.org)
  • Although anandamide (AEA) had been measured in human follicular fluid and is suggested to play a role in ovarian follicle and oocyte maturity, its exact source and role in the human ovary remains unclear. (jove.com)
  • The ENaC channel allows the flow of sodium from the lumen into the epithelial cell and modulates the amount of sodium in the extracellular fluid [ 2 ]. (hindawi.com)
  • Epithelial sodium channels ENaC that are specifically expressed along the entire length of cilia apparently serve as sensors that regulate fluid level surrounding the cilia. (rug.nl)
  • Studies of ion channels and ion transport involved in gland fluid transport. (stanford.edu)
  • The expression pattern of ASIC subunits is less well documented in humans, where ASIC3 ( 10 ⇓ - 12 ) has three variants differing in their C-termini ( 2 ). (pnas.org)
  • In this review, we will discuss recent studies showing the role of ENaC and ASIC channels in epithelial cells and its relationship to the oncogenesis. (jcancer.org)
  • The ENaC/DEG family includes structurally related acid-sensing ion channels (ASIC). (jcancer.org)
  • In this review, we will discuss the expression of the ENaC and ASIC channels in tumor cells and their role in tumor development and progression, and highlights them as potential new targets for cancer therapy in the future. (jcancer.org)
  • We find that ASIC‐1, a member of the degenerin/epithelial sodium channel family, which localizes at presynaptic terminals of dopaminergic neurons, is required for associative learning in C. elegans . (embopress.org)
  • Here, we present evidence that ASIC‐1, a new member of the DEG/ENaC family, contributes to sustain enhanced dopaminergic neurotransmission, necessary for associative learning in C. elegans . (embopress.org)
  • It is generally believed that a vanilloid receptor subtype-1 (VR1) and an acid-sensing ion channel (ASIC) mediate the greater part of acid-induced nociception in mammals. (semanticscholar.org)
  • Our data indicate that ENaC-mediated sodium entry may be the rate-limiting step in proteinuric sodium retention. (uzh.ch)
  • The epithelial sodium channel (ENaC) is typically localized in the apical membrane of epithelial cells. (arvojournals.org)
  • Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. (genecards.org)
  • We found that this interaction preserved the activity of the Sgk1-stimulated ENaC-dependent Na+ current while disrupting the interaction decreased ENaC density on the Xenopus laevis oocytes surface possibly by enhancing Nedd4-2-mediated ubiquitination that leads to ENaC degradation. (proteopedia.org)
  • Quantitative real-time PCR was used to investigate the expression of α-, β-, γ-, and δ-ENaC transcripts in ocular tissues. (sigmaaldrich.com)
  • At the mRNA level, all four ENaC subunits were found to be expressed in a wide range of ocular tissues from normal and glaucomatous human eyes, with the cornea, ciliary body, iris, and retina showing the highest expression levels. (sigmaaldrich.com)
  • There are several reports that ENaC is also present in ocular tissues and possibly linked with glaucoma. (arvojournals.org)
  • This should lead to a better understanding of the roles of these channels in different tissues. (phys.org)
  • To study the mechanisms by which these organisms survive on and inside respiratory tissues, a model in which successful long-term co-culture of bacteria and human cells can be performed is required. (jove.com)
  • We use primary human respiratory epithelial tissues raised to the air-liquid interface, the EpiAirway model (MatTek, Ashland, MA). (jove.com)
  • This necessitates special considerations, since both bacteria and primary human tissues are used in the same biosafety cabinet, and are co-cultured for extended periods. (jove.com)
  • The epithelial sodium channel (ENaC) is expressed in epithelial cells of several tissues involved in salt and water reabsorption. (biomedcentral.com)
  • Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells. (elsevier.com)
  • Serum- and glucocorticoid-regulated kinase isoform-1 and epithelial sodium channel subunits in human ocular ciliary epithelium. (semanticscholar.org)
  • Conserved charged residues at the surface and interface of epithelial sodium channel subunits - roles in cell surface expression and the sodium sel. (growkudos.com)
  • S. Guggino , Cyclic-Nucleotide Gated Cation Channels Contribute to Sodium Absorption in Lung: Role of Non-Selective Cation Channels. (elsevier.com)
  • These channels are heteromeric complexes consisting of 3 subunits: alpha, beta, and gamma. (genecards.org)
  • In addition, a heteromeric association between this member and ACCN3 (variant 1) has been observed to co-assemble into proton-gated channels sensitive to gadolinium. (wikidoc.org)
  • The human ENaC (epithelial sodium channel), a complex of three subunits, provides the rate-limiting step for sodium uptake in the distal nephron, and therefore plays a key role in salt homoeostasis and in regulating blood pressure. (biochemj.org)
  • The renal distal nephron plays an important role in the maintenance of sodium balance, extra cellular volume and blood pressure. (biomedcentral.com)
  • Because the mutant mice show preserved renal ENaC activity, this study provides evidence that the late distal convoluted tubule and early CNT can compensate to a large extent deficient ENaC-mediated sodium reabsorption in late CNT and CD. (asnjournals.org)
  • Both modes are inhibited by the APETx2 toxin, an ASIC3-type channel inhibitor. (pnas.org)
  • P-321 is a small molecule inhibitor of ENaC with an IC 50 of 1.9±0.75 nM in human epithelial cells. (arvojournals.org)
  • Parion may also receive an additional $230 million in development and regulatory milestones should Vertex elect to develop an additional ENaC inhibitor from Parion's research program. (cnbc.com)
  • These experiments also revealed that the new inhibitor interacts most effectively with the delta/beta/gamma ENaC. (phys.org)
  • We show that hASIC3 channels (hASIC3a, hASIC3b, or hASIC3c) are able to directly sense extracellular pH changes not only during acidification (up to pH 5.0), but also during alkalization (up to pH 8.0), an original and inducible property yet unknown. (pnas.org)
  • The alkaline sensitivity of hASIC3 is an intrinsic property of the channel, which is supported by the extracellular loop and involves two arginines (R68 and R83) only present in the human clone. (pnas.org)
  • Acid-sensing ion channels (ASICs) are depolarizing cationic channels gated by extracellular protons ( 1 ⇓ - 3 ). (pnas.org)
  • In such acidotic states, extracellular protons provoke the pain by opening cation channels in nociceptors. (semanticscholar.org)
  • The present invention concerns non-human transgenic animals that are useful as models of lung diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis. (google.com)
  • Animal models and in vivo human studies have also demonstrated an important role for the neutrophil in mediating lung damage in CF, but have not established whether this is a primary or secondary phenomenon. (ersjournals.com)
  • 15 showed that sterile human fetal CF small airway grafts implanted into severe combined immunodeficiency mice developed neutrophil-mediated inflammatory changes, leading to progressive lung tissue destruction: matched non-CF grafts did not suffer this fate. (ersjournals.com)
  • Lung pathology in cystic fibrosis is linked to dehydration of the airways epithelial surface which in part results from inappropriately raised sodium reabsorption through the epithelial sodium channel (ENaC). (cfgenetherapy.org.uk)
  • The studies were conducted in the endothelial cells that line human lung capillaries, known to form a tight barrier for the blood vessels. (eurekalert.org)
  • A troubled lung also becomes acidic, which can activate this acid sensing ion channel. (eurekalert.org)
  • The mRNA expression of ENaC and Na + -K + -ATPase subunits was tested in the lung by Northern blot following a 3 hours to 14 days infection. (biomedcentral.com)
  • Several lines of evidence suggest that up-regulation or downregulation of ENaC activity in the lung could be associated with lung infection. (biomedcentral.com)
  • Promotes stability and cell surface expression of epithelial sodium channel (ENAC) subunits SCNN1A and SCNN1G (By similarity). (abcam.com)
  • Exons 13 of Scnn1a and Scnn1b , which encode the second transmembrane segment and the COOH termini of α- and β-ENaC, respectively, were amplified from pooled DNA samples of members of each family by PCR. (aaccjnls.org)
  • In rodent sensory neurons, acid-sensing ion channel 3 (ASIC3) has recently emerged as a particularly important sensor of nonadaptive pain associated with tissue acidosis. (pnas.org)
  • They also found at work in the barrier function, a hybrid of ENaC-alpha and the acid sensing ion channel, known for its pain-mediating contributions in the brain. (eurekalert.org)
  • PLUNC's ability to regulate ENaC is pH-sensitive and fails in acidic cystic fibrosis airways. (wikipedia.org)
  • Thus, the transport of water and sodium is changed both via the aquaporin 2 water channels and the epithelial sodium channels during all three types of volume expansion to regulate and maintain water- and sodium homeostasis in the body. (biomedcentral.com)
  • sgk: an essential convergence point for peptide and steroid hormone regulation of ENaC-mediated Na+ transport. (semanticscholar.org)
  • Our results showed that high sodium decreased AMP-activated kinase (AMPK) phosphorylation in endothelial cells. (emory.edu)
  • Insulin-stimulated trafficking of ENaC in renal cells requires PI 3-kinase activity. (semanticscholar.org)
  • Henke G, Maier G, Wallisch S, Boehmer C, Lang F. Regulation of the voltage gated K+ channel Kv1.3 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid inducible kinase SGK1. (proteopedia.org)
  • Human SCNN1 was assigned to chromosome 12 using the NIGMS hybrid mapping panel 2. (tcdb.org)
  • Epithelial sodium channel (ENaC), which consists of three homologous subunits ( α , β and γ ) plays an important role in Na + reabsorption in kidneys ( Warnock & Rossier , 2005 ). (peerj.com)
  • To date, the information with regard to effect of testosterone on ENaC expression in kidneys were far from complete. (peerj.com)
  • Because AQP2 and ENaC plays such an important role in water and sodium balance and associated disorders, it is important to identify factors involved in the reabsorption of water and sodium by the kidneys in order to study these disorders in the future. (biomedcentral.com)
  • Increased sodium reabsorption, and since water follows sodium it also increases water reabsorption in kidneys. (answers.com)
  • These findings were not associated with significant differences in airway hydration or ciliary beating frequency, whereas experiments in cultured human airway epithelial cells (which contained no gland) showed that cigarette smoke exposure for 24 h was associated with reduced mucus hydration (as shown by reduced airway surface liquid depth), reduced ciliary beating frequency and reduced mucociliary transport. (ersjournals.com)
  • Modulation of acid-sensing ion channels: molecular mechanisms and therapeutic potential. (semanticscholar.org)
  • Heteromultimers of DEG/ENaC subunits form H+-gated channels in mouse sensory neurons. (semanticscholar.org)
  • Although ENaC typically has Na+ transport roles, it is also involved in the cell volume regulation of rat hepatocytes. (ovid.com)
  • The number of active sodium channel complexes present at the plasma membrane appears to be tightly controlled. (biochemj.org)
  • The ENaC expression at plasma membrane requires the regulated transport, processing, and macromolecular assembly in a defined and highly compartmentalized manner. (cheric.org)
  • All cells use a complex array of ion channels to maintain the appropriate ionic gradients across membrane barriers, including the plasma membrane and intracellular compartments and organelles. (g3journal.org)