Ion Channels
Ion Channel Gating
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.
Acid Sensing Ion Channels
Calcium Channels
Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.
Potassium Channels, Inwardly Rectifying
Chloride Channels
Potassium Channel Blockers
Calcium Channel Blockers
Potassium Channels, Voltage-Gated
Ligand-Gated Ion Channels
Calcium Channels, L-Type
Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.
Potassium Channels, Calcium-Activated
KATP 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.
Electrophysiology
Shaker Superfamily of Potassium Channels
Cyclic Nucleotide-Gated Cation Channels
Sodium Channel Blockers
Membrane Potentials
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).
TRPC Cation Channels
Patch-Clamp Techniques
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.
Large-Conductance Calcium-Activated Potassium Channels
TRPM Cation Channels
Ion Transport
Xenopus laevis
TRPV Cation Channels
Calcium Channels, N-Type
Oocytes
Calcium Channels, T-Type
Kv1.2 Potassium Channel
Epithelial Sodium Channels
Transient Receptor Potential Channels
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.
Ether-A-Go-Go Potassium Channels
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.
Potassium
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.
Kv1.3 Potassium Channel
Molecular Sequence Data
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.
Amino Acid Sequence
Kv1.1 Potassium Channel
Kv1.5 Potassium Channel
Xenopus
Calcium
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.
KCNQ Potassium Channels
Cell Membrane
Calcium Channel Agonists
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.
Shab Potassium Channels
Sodium Channels
Kv1.4 Potassium Channel
Models, Molecular
Sodium
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Neurons
Small-Conductance Calcium-Activated Potassium Channels
Action Potentials
Protein Structure, Tertiary
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.
Cations
Shaw Potassium Channels
Lipid Bilayers
Shal Potassium Channels
Protein Subunits
Cells, Cultured
Degenerin Sodium Channels
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.
Models, Biological
Mutation
Ions
Adenosine Triphosphate
NAV1.5 Voltage-Gated Sodium Channel
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Dose-Response Relationship, Drug
Acid Sensing Ion Channel Blockers
Potassium Channels
Gramicidin
Barium
KCNQ2 Potassium Channel
Hydrogen-Ion Concentration
Scorpion Venoms
Intermediate-Conductance Calcium-Activated Potassium Channels
Rats, Sprague-Dawley
Ryanodine Receptor Calcium Release Channel
A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.
Delayed Rectifier Potassium Channels
Binding Sites
Protein Conformation
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
HEK293 Cells
KCNQ3 Potassium Channel
Voltage-Gated Sodium Channels
NAV1.2 Voltage-Gated Sodium Channel
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.
Membrane Proteins
Calcium Channels, P-Type
Receptors, Nicotinic
One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.
Cell Membrane Permeability
Amiloride
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)
Charybdotoxin
Mutagenesis, Site-Directed
Alamethicin
Calcium Channels, R-Type
Sodium Channel Agonists
Voltage-Dependent Anion Channels
Anions
Transfection
Mechanotransduction, Cellular
Tetrodotoxin
Protein Structure, Secondary
Electrophysiological Phenomena
Protons
Protein Binding
Structure-Activity Relationship
Sulfonylurea Receptors
Receptors, Purinergic P2X2
A purinergic P2X neurotransmitter receptor involved in sensory signaling of TASTE PERCEPTION, chemoreception, visceral distension and NEUROPATHIC PAIN. The receptor comprises three P2X2 subunits. The P2X2 subunits also have been found associated with P2X3 RECEPTOR subunits in a heterotrimeric receptor variant.
Magnesium
Myocardium
Peptides
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Receptors, Drug
4-Aminopyridine
CHO Cells
Channelopathies
Heavy Ions
Cesium
NAV1.4 Voltage-Gated Sodium Channel
Amantadine
An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake.
Sequence Homology, Amino Acid
Nifedipine
Receptors, Serotonin, 5-HT3
Cricetinae
Dihydropyridines
Ion Pumps
Signal Transduction
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Amino Acid Substitution
The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.
Guinea Pigs
Rabbits
Receptors, Glycine
Ganglia, Spinal
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.
Myocytes, Cardiac
Rats, Wistar
NAV1.8 Voltage-Gated Sodium Channel
Apamin
Cations, Monovalent
Receptors, Purinergic P2X
Permeability
RNA, Complementary
omega-Conotoxin GVIA
Large-Conductance Calcium-Activated Potassium Channel beta Subunits
RNA, Messenger
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Ligands
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Long QT Syndrome
A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.
Saxitoxin
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.
Cloning, Molecular
Cricetulus
Torpedo
Water
Quaternary Ammonium Compounds
Cystic Fibrosis Transmembrane Conductance Regulator
Receptors, Purinergic P2
Phosphatidylinositol 4,5-Diphosphate
A phosphoinositide present in all eukaryotic cells, particularly in the plasma membrane. It is the major substrate for receptor-stimulated phosphoinositidase C, with the consequent formation of inositol 1,4,5-triphosphate and diacylglycerol, and probably also for receptor-stimulated inositol phospholipid 3-kinase. (Kendrew, The Encyclopedia of Molecular Biology, 1994)
Porosity
Sensory Receptor Cells
Models, Chemical
Mechanoreceptors
Pinacidil
Protein Isoforms
Cyclic GMP
Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)
Glutamic Acid
Sarcolemma
Protein Transport
Spider Venoms
Batrachotoxins
Hippocampus
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
Recombinant Fusion Proteins
DNA, Complementary
Conotoxins
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)
Mibefradil
Cation Transport Proteins
Receptors, Cholinergic
Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology.
Sequence Alignment
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
omega-Conotoxins
Receptors, Purinergic P2X4
Electrochemistry
Kidney
Brain
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
Connexins
NAV1.1 Voltage-Gated Sodium Channel
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.
Aquaporins
Tetraethylammonium block of the BNC1 channel. (1/363)
The brain Na+ channel-1 (BNC1, also known as MDEG1 or ASIC2) is a member of the DEG/ENaC cation channel family. Mutation of a specific residue (Gly430) that lies N-terminal to the second membrane-spanning domain activates BNC1 and converts it from a Na+-selective channel to one permeable to both Na+ and K+. Because all K+ channels are blocked by tetraethylammonium (TEA), we asked if TEA would inhibit BNC1 with a mutation at residue 430. External TEA blocked BNC1 when residue 430 was a Val or a Thr. Block was steeply voltage-dependent and was reduced when current was outward, suggesting multi-ion block within the channel pore. Block was dependent on the size of the quaternary ammonium; the smaller tetramethylammonium blocked with similar properties, whereas the larger tetrapropylammonium had little effect. When residue 430 was Phe, the effects of tetramethylammonium and tetrapropylammonium were not altered. In contrast, block by TEA was much less voltage-dependent, suggesting that the Phe mutation introduced a new TEA binding site located approximately 30% of the way across the electric field. These results provide insight into the structure and function of BNC1 and suggest that TEA may be a useful tool to probe function of this channel family. (+info)Paradoxical stimulation of a DEG/ENaC channel by amiloride. (2/363)
Extracellular amiloride inhibits all known DEG/ENaC ion channels, including BNC1, a proton-activated human neuronal cation channel. Earlier studies showed that protons cause a conformational change that activates BNC1 and exposes residue 430 to the extracellular solution. Here we demonstrate that, in addition to blocking BNC1, amiloride also exposes residue 430. This result suggested that, like protons, amiloride might be capable of activating the channel. To test this hypothesis, we introduced a mutation in the BNC1 pore that reduces amiloride block, and found that amiloride stimulated these channels. Amiloride inhibition was voltage-dependent, suggesting block within the pore, whereas stimulation was not, suggesting binding to an extracellular site. These data show that amiloride can have two distinct effects on BNC1, and they suggest two different interaction sites. The results suggest that extracellular amiloride binding may have a stimulatory effect similar to that of protons in BNC1 or extracellular ligands in other DEG/ENaC channels. (+info)Cloning and functional expression of a novel degenerin-like Na+ channel gene in mammals. (3/363)
1. A degenerate polymerase chain reaction (PCR) homology screening procedure was applied to rat brain cDNA in order to identify novel genes belonging to the amiloride-sensitive Na+ channel and degenerin (NaC/DEG) family of ion channels. A single gene was identified that encodes a protein related to but clearly different from the already cloned members of the family (18-30 % amino acid sequence identity). Phylogenetic analysis linked this protein to the group of ligand-gated channels that includes the mammalian acid-sensing ion channels and the Phe-Met-Arg-Phe-amide (FMRFamide)-activated Na+ channel. 2. Expression of gain-of-function mutants after cRNA injection into Xenopus laevis oocytes or transient transfection of COS cells induced large constitutive currents. The activated channel was amiloride sensitive (IC50, 1.31 microM) and displayed a low conductance (9-10 pS) and a high selectivity for Na+ over K+ (ratio of the respective permeabilities, PNa+/PK+ >= 10), all of which are characteristic of NaC/DEG channel behaviour. 3. Northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed a predominant expression of its mRNA in the small intestine, the liver (including hepatocytes) and the brain. This channel has been called the brain-liver-intestine amiloride-sensitive Na+ channel (BLINaC). 4. Corresponding gain-of-function mutations in Caenorhabditis elegans degenerins are responsible for inherited neurodegeneration in the nematode. Besides the BLINaC physiological function that remains to be established, mutations in this novel mammalian degenerin-like channel might be of pathophysiological importance in inherited neurodegeneration and liver or intestinal pathologies. (+info)Molecular cloning, functional expression and chromosomal localization of an amiloride-sensitive Na(+) channel from human small intestine. (4/363)
Amiloride-sensitive Na(+) channels belonging to the recently discovered NaC/DEG family of genes have been found in several human tissues including epithelia and central and peripheral neurons. We describe here the molecular cloning of a cDNA encoding a novel human amiloride-sensitive Na(+) channel subunit that is principally expressed in the small intestine and has been called hINaC (human intestine Na(+) channel). This protein is similar to the recently identified rodent channel BLINaC and is relatively close to the acid sensing ion channels (ASICs) (79 and 29% amino acid identity, respectively). ASICs are activated by extracellular protons and probably participate in sensory neurons to nociception linked to tissue acidosis. hINaC is not activated by lowering the external pH but gain-of-function mutations can be introduced and reveal when expressed in Xenopus oocytes, an important Na(+) channel activity which is blocked by amiloride (IC(50)=0.5 microM). These results suggest the existence of a still unknown physiological activator for hINaC (e.g. an extracellular ligand). The presence of this new amiloride-sensitive Na(+) channel in human small intestine probably has interesting physiological as well as physiopathological implications that remain to be clarified. The large activation of this channel by point mutations may be associated with a degenerin-like behavior as previously observed for channels expressed in nematode mechanosensitive neurons. The hINaC gene has been mapped on the 4q31.3-q32 region of the human genome. (+info)Neuropeptide FF and FMRFamide potentiate acid-evoked currents from sensory neurons and proton-gated DEG/ENaC channels. (5/363)
Acidosis is associated with inflammation and ischemia and activates cation channels in sensory neurons. Inflammation also induces expression of FMRFamidelike neuropeptides, which modulate pain. We found that neuropeptide FF (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe amide) and FMRFamide (Phe-Met-Arg-Phe amide) generated no current on their own but potentiated H+-gated currents from cultured sensory neurons and heterologously expressed ASIC and DRASIC channels. The neuropeptides slowed inactivation and induced sustained currents during acidification. The effects were specific; different channels showed distinct responses to the various peptides. These results suggest that acid-sensing ion channels may integrate multiple extracellular signals to modify sensory perception. (+info)Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels. (6/363)
Acid sensing is associated with nociception, taste transduction, and perception of extracellular pH fluctuations in the brain. Acid sensing is carried out by the simplest class of ligand-gated channels, the family of H(+)-gated Na(+) channels. These channels have recently been cloned and belong to the acid-sensitive ion channel (ASIC) family. Toxins from animal venoms have been essential for studies of voltage-sensitive and ligand-gated ion channels. This paper describes a novel 40-amino acid toxin from tarantula venom, which potently blocks (IC(50) = 0.9 nm) a particular subclass of ASIC channels that are highly expressed in both central nervous system neurons and sensory neurons from dorsal root ganglia. This channel type has properties identical to those described for the homomultimeric assembly of ASIC1a. Homomultimeric assemblies of other members of the ASIC family and heteromultimeric assemblies of ASIC1a with other ASIC subunits are insensitive to the toxin. The new toxin is the first high affinity and highly selective pharmacological agent for this novel class of ionic channels. It will be important for future studies of their physiological and physio-pathological roles. (+info)Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+. (7/363)
Proton receptors of the acid-sensing ion channel (ASIC) family are expressed in sensory neurons and thus could play a critical role in the detection of noxious acidosis. To investigate the subunit composition of native ASICs in peripheral and central neurons, we co-injected human as well as rodent ASIC2a and ASIC3 subunits in Xenopus oocytes. The amplitudes of acid-induced biphasic responses mediated by co-expressed ASIC2a and ASIC3 subunits were much larger (as much as 20-fold) than the currents mediated by the respective homomers, clearly indicating functional association. The reversal potential of the ASIC2a+3 current (>/=+20 mV) reflected a cationic current mainly selective for sodium. The sensitivity to pH or amiloride of single versus co-expressed ASIC subunits was not significantly different; however, gadolinium ions inhibited ASIC3 and ASIC2a+3 responses with much higher potency (IC(50) approximately 40 microm) than the ASIC2a response (IC(50) >/=1 mm). Biochemical interaction between ASIC2a and ASIC3 subunits was demonstrated by co-purification from transfected human embryonic kidney (HEK293) cells and Xenopus oocytes. Our in situ hybridization data showed that rat ASIC2a and ASIC3 transcripts are co-localized centrally, whereas reverse transcription-polymerase chain reaction data led us to detect co-expression of human ASIC2a and ASIC3 subunits in trigeminal sensory ganglia, brain, and testis where they might co-assemble into a novel subtype of proton-gated channels sensitive to gadolinium. (+info)A novel strategy for cancer therapy by mutated mammalian degenerin gene transfer. (8/363)
Mammalian degenerin (MDEG) is a member of the amiloride-sensitive sodium ion channel family, and its site-directed active mutant (MDEG-G430F) induces massive Na+ influx into cells, leading to cell ballooning and cell bursting. We attempted a novel therapeutic approach for gastric cancers by transferring MDEG-G430F into cancer cells using tumor-specific promoters. In carcinoembryonic antigen (CEA)-producing gastric cancer cells, the level of cell death observed when MDEG-G430F was used with a CEA promoter was similar to that observed when using a potent nonspecific promoter such as the cytomegalovirus promoter. In an in vivo study, fusogenic liposome complexes containing MDEG-G430F driven by the CEA promoter were injected intraperitoneally into CEA-producing gastric cancer cells in a mouse peritoneal dissemination model. Although all 15 of the control mice were dead by 50 days postinoculation, 13 of the 15 mice treated with MDEG-G430F survived. These results indicate that transferring MDEG-G430F into cancer tissues using tumor-specific promoters can achieve striking and selective cancer cell death irrespective of the transcriptional efficiency of the promoters used in vivo, and suggest that this approach is a promising new strategy for cancer gene therapy. (+info)
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ASICsASIC1ANeuronsExtracellularSubunitENaCASIC1ASIC2Cation channelsProteinsInhibitionNeuronalPharmacologySensorySubunitsASIC3BlockersCurrentsSuperfamilyPotentiates acid-senTransmembraneInhibitorProteinInhibits acid-senAmiloride-sensitive cationPeptidesMechanismsPhysiologicalInhibitorsPeptideFunctionalSelectivityModulation2017GenePeripheralExpression2016NociceptorsModulateSynapticMeSHAmino acidActivatesActivateIntracellularHuman Acid-sensing IonChicken acid-sensing ionPoreReceptorsASIC ChannelAcidicTherapeuticNociception
ASICs42
- Acid-sensing ion channels (ASICs) are permeable to Na + (and other cations), activated by low extracellular pH and widely expressed in the CNS and the peripheral nervous system (PNS). (nature.com)
- In large part, this question has driven increasing investigation on acid-sensing ion channels (ASICs) in the CNS and the peripheral nervous system for the past two decades. (nature.com)
- Acid-sensing ion channels (ASICs) are proton-gated cation channels that are predominantly expressed in the nervous system. (nih.gov)
- ASICs are involved in a number of neurological diseases such as pain, ischemic stroke and multiple sclerosis but limited tools are available to target these channels and provide probes for their physiological functions. (nih.gov)
- Acid-sensing ion channels (ASICs) are neuronal voltage-insensitive sodium channels activated by extracellular protons permeable to Na+. (wikipedia.org)
- Acid-sensing ion channels (ASICs) are proton-gated ion channels that are highly expressed in the nervous system and play important roles in physiological and pathological conditions. (intechopen.com)
- One of the candidate targets for proton sensing is called "acid-sensing ion channels" (ASICs). (intechopen.com)
- Acid-Sensing Ion Channels (ASICs) are membrane protein complexes that form depolarizing ion channels present on peripheral and/or central neurons. (springer.com)
- Voiley N (2004) Acid-sensing ion channels (ASICs): new targets for the analgesic effects of non-steroid anti-inflammatory drugs (NSAIDs). (springer.com)
- Acid-sensing ion channels (ASICs) are voltage-independent, amiloride-sensitive channels involved in diverse physiological processes ranging from nociception to taste. (rcsb.org)
- These studies define mechanisms for activation of ASICs, illuminate the basis for dynamic ion selectivity and provide the blueprints for new therapeutic agents. (rcsb.org)
- Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. (jneurosci.org)
- The results provide the first evidence that ASICs may contribute to chemotransduction of low pH by carotid body chemoreceptors, and that extracellular acidosis directly activates carotid body chemoreceptors through both ASIC and TASK channels. (ahajournals.org)
- Acid-sensing ion channels (ASICs) are epithelial Na + channels gated by external H + . Recently, it has been demonstrated that ASICs play a role in Na + uptake in freshwater rainbow trout. (biologists.org)
- ASICs are H + -gated Na + channels that belong to the epithelial Na + channel/degenerin (ENaC/DEG) superfamily (for a review, see Holzer, 2009 ). (biologists.org)
- The acid-sensing ion channels (ASICs) are a family of ion channels expressed throughout the mammalian nervous system. (aspetjournals.org)
- However, not all ASICs are proton-sensitive: ASIC2a is activated by acid, whereas its splice variant ASIC2b is not. (aspetjournals.org)
- One important regulator of acid-sensing ion channels (ASICs) is zinc. (nih.gov)
- Increased extracellular proton concentrations during neurotransmission are converted to excitatory sodium influx by acid-sensing ion channels (ASICs). (elifesciences.org)
- 10-fold sodium/potassium selectivity in ASICs has long been attributed to a central constriction in the channel pore, but experimental verification is lacking due to the sensitivity of this structure to conventional manipulations. (elifesciences.org)
- Acid-sensing ion channels (ASICs) are neuronal receptors for extracellular protons. (aspetjournals.org)
- In summary, our results show that diminazene blocks ASIC1a by a slow open-channel block and suggest that diminazene is an interesting lead compound for high-affinity blockers of ASICs. (aspetjournals.org)
- Acid-sensing ion channels (ASICs) are proton-gated cation channels that are involved in diverse neuronal processes including pain sensing. (elifesciences.org)
- Acid-sensing (proton-gated) ion channels (ASICs): ASIC3. (guidetopharmacology.org)
- Acid-sensing ion channels( ASICs) are proton-gated channels expressed widely in the central nervous systems and peripheral tissues,among which ASIC1 a is a core part and plays an important role in many physiological and pathological processes. (cnki.com.cn)
- The acid-sensing ion channels (ASICs), which can be activated by acute drops in the extracellular pH, play an important role in nociception. (springer.com)
- ASICs are implicated in neurotransmission, synaptic plasticity, learning, ischaemia and neuronal cell death and contribute to perception of acid‐mediated inflammatory or post‐operative pain (Wemmie et al. (deepdyve.com)
- Recently, the blockade of acid-sensing ion channels (ASICs) with amiloride and A-316567 attenuated the reflex. (elsevier.com)
- Acid-sensing ion channels (ASICs) are voltage-independent, proton-activated receptors that belong to the epithelial sodium channel/degenerin family of ion channels and are implicated in perception of pain, ischaemic stroke, mechanosensation, learning and memory. (diff.org)
- Acid sensing ion channels (ASICs) are proton-gated cation channels expressed in both central and peripheral nervous systems. (semanticscholar.org)
- In disease states, tissue acidosis is a common pathologic change causing abnormal activation of acid-sensing ion channels (ASICs), which according to cumulative evidence, significantly contributes to inflammation, mitochondrial dysfunction, and other pathologic mechanisms (i.e., pain, stroke, and psychiatric conditions). (biomedcentral.com)
- ASICs are ligand-gated cation channels activated by extracellular H + and are widely distributed in mammalian central and peripheral nervous systems. (biomedcentral.com)
- Acid-sensing ion channels (ASICs) are proton-gated Na+ channels. (oxfordhandbooks.com)
- Acid-sensing ion channels (ASICs) are densely expressed in broad areas of mammalian brains and actively modulate synaptic transmission and a variety of neuronal activities. (nebraska.edu)
- Little is known about the function of acid-sensing ion channels (ASICs) in bone cells or osteoporotic vertebral fractures (OVF). (elsevier.com)
- Acid-sensing ion channels (ASICs) are a family of ion channels comprised of six subunits encoded by four genes and they are expressed throughout the peripheral and central nervous systems. (biomedcentral.com)
- Unlike mice and humans, naked mole-rats do not perceive acid as a noxious stimulus, even though their sensory neurons express functional ASICs, likely an adaptation to living in a hypercapnic subterranean environment. (biomedcentral.com)
- Acid-sensing ion channels (ASICs) are a group of six ion channels encoded by four different genes, splice variants of the genes encoding ASIC1 and ASIC2 produce ASIC1a and ASIC1b, and ASIC2a and ASIC2b respectively [ 1 ]. (biomedcentral.com)
- Objective To study the expression and significance of acid-sensing ion channels (ASICs)in rat articular cartilage with adjuvant arthritis . (bvsalud.org)
- Acid-sensing ion channels (ASICs) are members of the degenerin/epithelial Na + channel family of non-voltage-gated cation channels ( 1 - 3 ). (pnas.org)
- These proteins (called ''acid-sensing ion channels', or ASICs) stimulate neurons when increased acid is detected. (scientificamerican.com)
- Acid- sensing ion channels (ASICs) are key sensors for extracellular protons and contribute to pain caused by tissue acidosis. (chinaphar.com)
ASIC1A32
- In the CNS, the ASIC1A subunit is largely required for acid-evoked currents and has been implicated in synaptic plasticity, mouse models of behaviour, neurodegenerative diseases, cancer and seizures. (nature.com)
- Until now, six different isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) in rodents have been discovered and they can be assembled into homotrimers or heterotrimers to form an ion channel. (intechopen.com)
- The human ACCN2 gene encodes the pore-forming subunit of ASIC1a, a proton-activated, channel permeable to both Na+ and Ca2+ ions. (criver.com)
- ASIC1a channels widely expressed in the neurons of peripheral sensory and the central nervous system are therapeutic targets in pain and neurodegenerative diseases. (criver.com)
- Acid-sensing ion channel 1a (ASIC1a) is the primary acid sensor in mammalian brain and a key mediator of acidosis-induced neuronal damage following cerebral ischemia. (pnas.org)
- Crystal structures of ASIC1a-psalmotoxin complexes map the toxin binding site to the extracellular domain and show how toxin binding triggers an expansion of the extracellular vestibule and stabilization of the open channel pore. (rcsb.org)
- Manipulating ASIC1a expression in striatal neurons in mice revealed that this channel is critical for promoting the synaptic abundance and function of NMDA receptors in response to changes in extracellular pH. (sciencemag.org)
- By activating a kinase-dependent transcriptional program that promotes the expression of NMDA receptor subunits, ASIC1a channels stimulate synaptic activity and dendritic spine maturation in the striatal neurons that facilitate motor learning. (sciencemag.org)
- Acid-sensing ion channel 1a (ASIC1a) is abundant in multiple brain regions, including the striatum, which serves as the input nucleus of the basal ganglia and is critically involved in procedural learning and motor memory. (sciencemag.org)
- Acid-sensing ion channel-1a (ASIC1a) is a potential therapeutic target for multiple neurological diseases. (jneurosci.org)
- We studied here ASIC1a glycosylation and trafficking, two poorly understood processes pivotal in determining the functional outcome of an ion channel. (jneurosci.org)
- Inhibiting glycosylation with tunicamycin reduced ASIC1a surface trafficking, dendritic targeting, and acid-activated current density. (jneurosci.org)
- ASIC1a glycosylation further regulates ASIC1a pH sensitivity and acid-activated current density. (jneurosci.org)
- The Human Acid-Sensing Ion Channel ASIC1a: Evidence for a Homotetrameric Assembly State at the Cell Surface. (sigmaaldrich.com)
- The expression of ASIC1a monomers, trimeric or tetrameric concatemeric cDNA constructs resulted in functional channels. (sigmaaldrich.com)
- Our data identify a major ASIC1a homotetramer at the surface membrane of the cell expressing functional ASIC1a channel. (sigmaaldrich.com)
- Here, we have replaced the main chain amide carbonyl of G10' with an ester carbonyl in ASIC1a, which unlike conventional mutagenesis, allowed us to measure function in channels with alterations to the G10' main chain oxygen. (elifesciences.org)
- Via extensive mutagenesis, further unnatural amino acid incorporation and engineered subunit stoichiometry, we established that a band of negatively charged side chains at the lower end of the channel pore enables preferential Na + conductance, revealing the molecular basis for excitatory ASIC1a function. (elifesciences.org)
- Duan B et al (2007) Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity. (springer.com)
- Acid-sensing ion channel 1a (ASIC1a) is a primary acid sensor in the peripheral and central nervous system. (edu.au)
- Five subunits (ASIC1a, ASIC1 b, ASIC2 a, ASIC3 b and ASIC3 ) can combine to form acid-activated channels. (diff.org)
- The human ortholog of acid-sensing ion channel gene ASIC1a is associated with panic disorder and amygdala structure and function. (rush.edu)
- Na + ,Ca 2+ -permeable acid-sensing ion channel 1a (ASIC1a) is involved in the pathophysiologic process of adult focal brain ischemia. (elsevier.com)
- External application of 1 mM Ni(2+) rapidly inhibited homomeric ASIC1a and heteromeric ASIC1a/2a channels without affecting ASIC1b, 2a, and ASIC3 homomeric channels and ASIC1a/3 and 2a/3 heteromeric channels. (qxmd.com)
- In contrast, external Cd(+) (1 mM) inhibited ASIC2a and ASIC3 homomeric channels and ASIC1a/2a, 1a/3, and 2a/3 heteromeric channels but not ASIC1a homomeric channels. (qxmd.com)
- The acid-sensing current in isolated rat hippocampus CA1 neurons, thought to be carried primarily by ASIC1a and 1a/2a, was inhibited by 1 mM Ni(2+). (qxmd.com)
- Purpose: The purpose of the current study is to assess changes in the expression of Acid-Sensing Ion Channel (ASIC)1a and ASIC2 in retinal ganglion cells (RGCs) after retinal ischemia and reperfusion (I/R) injury and to test if inhibition of ASIC1a provides RGC neuroprotection. (unthsc.edu)
- Acid-sensing ion channel-1a (ASIC1a) is localized in brain regions with high synaptic density and is thought to contribute to synaptic plasticity, learning, and memory. (stonel.info)
- The acid-sensing ion channel-1a (ASIC1a) is composed of 3 subunits and is activated by a decrease in extracellular pH. (pnas.org)
- These results indicate that channel function is controlled by disulfide bond formation between intracellular residues on distinct ASIC1a subunits. (pnas.org)
- Conversely, extracellular modification with a cysteine-oxidizing reagent 5,5′-dithiobis 2-nitrobenzoic acid (DTNB) decreased ASIC1a current ( 26 , 27 ). (pnas.org)
- Given the signaling role of H 2 O 2 and other oxidants in normal and abnormal brain function ( 22 , 28 ) and the importance of ASIC1a in diseases associated with oxidative stress, we asked how H 2 O 2 influences ASIC1a channel structure. (pnas.org)
Neurons24
- Why do neurons sense extracellular acid? (nature.com)
- 2002) Heteromultimers of DEG/ENaC Subunits Form H + -Gated Channels in Mouse Sensory Neurons. (springer.com)
- Mamet J, Lazdunski M, Voilley N (2003) How nerve growth factor drives physiological and inflammatory expressions of acid-sensing ion channel 3 in sensory neurons. (springer.com)
- 2001) Acid-Sensing Ion Channel 3 Matches the Acid-Gated Current in Cardiac Ischemia-Sensing Neurons. (springer.com)
- 1997a) Molecular Cloning of a Non-Inactivating Proton-Gated Na + Channel Specific for Sensory Neurons. (springer.com)
- We found that these channels can be activated in neurons of the medial nucleus of the trapezoid body (MNTB) of the auditory system in the CNS. (jneurosci.org)
- SIGNIFICANCE STATEMENT The manuscript demonstrates that postsynaptic neurons of the medial nucleus of the trapezoid body at the mouse calyx of Held synapse express functional homomeric Acid-sensing ion channel-1a (ASIC-1as) that can be activated by protons (coreleased with neurotransmitter from acidified synaptic vesicles). (jneurosci.org)
- Acid-sensing ion channel 1b (ASIC1b) is a proton-gated Na(+) channel mostly expressed in peripheral sensory neurons. (nih.gov)
- Fu H et al (2016) Acid-sensing ion channels in trigeminal ganglion neurons innervating the orofacial region contribute to orofacial inflammatory pain. (springer.com)
- Regulation of acid signaling in rat pulmonary sensory neurons by protease-activated receptor-2. (semanticscholar.org)
- Acid-sensing ion channels (ASIC) are ligand-gated cation channels that are highly expressed in peripheral sensory and central neurons. (qxmd.com)
- We demonstrate here that the heavy metals Ni(2+) and Cd(2+) dose-dependently inhibit ASIC currents in hippocampus CA1 neurons and in Chinese hamster ovary (CHO) cells heterologously expressing these channels. (qxmd.com)
- Functional characterization of acid-sensing ion channels in cultured neurons of rat inferior colliculus. (qxmd.com)
- Acid-sensing ion channel 2 (ASIC2) modulates ASIC1 H+-activated currents in hippocampal neurons. (qxmd.com)
- Characterization of acid-sensing ion channels in dorsal horn neurons of rat spinal cord. (qxmd.com)
- Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action. (qxmd.com)
- Acid-sensing ion channels (ASIC) are members of the ENaC/Deg (epithelial amiloride-sensitive Na+ channel and degenerin) family of ion channels and are widely expressed in neurons of the central and peripheral nervous system. (genecards.org)
- The Research Focus The Molecular Nociception Group focuses on genetic approaches to understanding the biology of damage-sensing neurons, somatosensation, pain and touch. (ucl.ac.uk)
- Within individual neurons, it localizes to the cell soma and to dendritic spines, where it mediates an acid-activated increase in [Ca 2+ ] i and regulates spine number ( 8 - 10 ). (pnas.org)
- Recent studies have demonstrated an important role for T-type Ca 2+ channels (T-channels) in controlling the excitability of peripheral pain-sensing neurons (nociceptors). (jneurosci.org)
- After injury, peripheral pain-sensing neurons (nociceptors) can become hyperexcitable, or "sensitized. (jneurosci.org)
- In current-clamp recording, pre-application with ET-1 (30 nM) significantly increased acid-evoked firing in rat DRG neurons. (chinaphar.com)
- G protein-gated ion channels are a family of transmembrane ion channels in neurons and atrial myocytes that are directly gated by G proteins. (wikipedia.org)
- G protein-gated ion channels are primarily found in CNS neurons and atrial myocytes, and affect the flow of potassium (K+), calcium (Ca2+), sodium (Na+), and chloride (Cl−) across the plasma membrane. (wikipedia.org)
Extracellular24
- Play media Each acid-sensing ion channel is composed of a 500-560 amino acid sequence, which is constructed into a six transmembrane segment-two per subunit (TMD1 and TMD2), a cytoplasmic amino-carboxyl termini, and a large extracellular domain. (wikipedia.org)
- TMD1 is connected to the β-sheets of the extracellular domain that flex to widen the extracellular domain to allow for ion passage through the channel. (wikipedia.org)
- The specific amino acid residue of aspartate on the extracellular side lumen of TMD2 in ASIC1 has been linked to the channel's low Ca2+ conductance. (wikipedia.org)
- Distinguished by its specific amino acid configurations, the extracellular region is fundamental to the induction of activation/inactivation along with pH gating. (wikipedia.org)
- Glycosylation is also apparent within the extracellular region, playing an important role in the trafficking the channel to the membrane's surface as well as establishing the ASIC's sensitivity to pH levels. (wikipedia.org)
- The role of the ASIC is to sense reduced levels of extracellular pH and result in a response or signal from the neuron. (wikipedia.org)
- The epithelial sodium channel/degenerin family encompasses a group of cation-selective ion channels that are activated or modulated by a variety of extracellular stimuli. (nih.gov)
- Recent findings have begun to elucidate the structural elements that allow these channels to sense and respond to extracellular factors. (nih.gov)
- This review emphasizes the roles of the extracellular domain in sensing changes in the extracellular milieu and of the residues in the extracellular-transmembrane domains interface in coupling extracellular changes to the pore of the channel. (nih.gov)
- Epithelial sodium channels and acid-sensing ion channels have evolved to sense extracellular cues. (nih.gov)
- These channels are opened by extracellular protons. (springer.com)
- Recently, pH-sensitive ion channels have been described in glomus cells that respond directly to extracellular acidosis. (ahajournals.org)
- In this study, we investigated the possible molecular mechanisms of carotid body pH-sensing by recording the responses of glomus cells isolated from rat carotid body to rapid changes in extracellular pH using whole-cell patch-clamping technique. (ahajournals.org)
- We made a series of chimeric ASIC2 proteins, and using whole-cell electrophysiology we have identified the minimal region of the ASIC2a extracellular domain that is required for ASIC2 proton activation: the first 87 amino acids after transmembrane domain 1. (aspetjournals.org)
- Changes in extracellular environment and chemical signals from adjacent cells are rapidly converted into electrical signals by ligand-gated ion channels in the cell membrane. (elifesciences.org)
- In such acidotic states, extracellular protons provoke the pain by opening cation channels in nociceptors. (semanticscholar.org)
- The structure of ASIC1 is characterized by subunit of the chalice-shaped homotrimer that is formed by a short amino and carboxy termini, two transmembrane helices, a bound chloride ion and a disulphide-rich, multidomain extracellular region enriched in acidic residues and carboxyl-carboxylate pairs within 3.0Å, suggesting that at least one carboxyl group bears a proton. (diff.org)
- The members of this family are amiloride-sensitive sodium channels that contain intracellular N and C termini, 2 hydrophobic transmembrane regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. (genecards.org)
- Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. (genecards.org)
- Here, we demonstrate that reducing agents as well as endogenous metal chelators sensitize C-type dorsal root ganglion nociceptors by chelating Zn 2+ ions off specific extracellular histidine residues on Ca v 3.2 T-channels, thus relieving tonic channel inhibition, enhancing Ca v 3.2 currents, and lowering the threshold for nociceptor excitability in vitro and in vivo . (jneurosci.org)
- We then demonstrate that the sensitization is facilitated through a novel mechanism, whereby reducing agents chelate Zn 2+ ions off specific extracellular histidine residues in domain I of Ca v 3.2, thereby relieving tonic channel inhibition. (jneurosci.org)
- Introduction: The acid-sensing ion channel (ASIC) is specifically activated by a drop in the extracellular pH level. (umsystem.edu)
- One type of Cl − channel is activated by extracellular acidic pH. (sciencemag.org)
- These ion channels, once activated, allow for the flow of potassium ions (K+) from the extracellular space surrounding the cell across the plasma membrane and into the cytoplasm. (wikipedia.org)
Subunit7
- A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells. (nature.com)
- Your search returned 13 acid sensing ion channel subunit 2 ELISA ELISA Kit across 2 suppliers. (biocompare.com)
- Subunit-dependent high-affinity zinc inhibition of acid-sensing ion channels. (qxmd.com)
- ASIC2 (Acid Sensing Ion Channel Subunit 2) is a Protein Coding gene. (genecards.org)
- ASIC4 (Acid Sensing Ion Channel Subunit Family Member 4) is a Protein Coding gene. (genecards.org)
- Behavioral acid insensitivity is accounted for by a genetic variation in the voltage-gated Na + channel subunit 1.7 (NaV1.7), which confers enhanced acid inhibition [ 14 ]. (biomedcentral.com)
- We therefore asked if H 2 O 2 regulated their formation, where the inter-subunit links occur, and how their formation affects the channel. (pnas.org)
ENaC12
- These four compounds (100 microM) failed to block ENaC channels expressed in oocytes. (nih.gov)
- ASIC proteins are a subfamily of the ENaC/Deg superfamily of ion channels. (wikipedia.org)
- a feature conserved in most vertebrate members of the overarching DEG/ENaC family of channels (named after invertebrate deg enerins and vertebrate e pithelial Na + c hannels). (elifesciences.org)
- This gene encodes a member of the acid-sensing ion channel (ASIC) family of proteins, which are part of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. (nih.gov)
- Acid sensing ion channels are voltage-indipendent, proton activated receptors that belong to the epithelial sodium channel (ENaC)/degenerin family of ion channels and are involved in perception of pain (and also ischaemic stroke, mechanosensation, even in learning and memory). (diff.org)
- ASIC channels belong to the ENaC/Degenerin superfamily and are proton-gated ion channels which are not voltage-dependent. (alomone.com)
- and identifying a compound that alters the activity of said acid-sensing ion channel of the DEG/ENaC family that is capable of treating acidosis or excess glutamate associated with seizures or strokes, wherein said acid-sensing ion channel mediates the effects of said acidosis or excess glutamate. (patentsencyclopedia.com)
- and detecting a change in activity of said acid-sensing ion channels of the DEG/ENaC family, thereby identifying said compound that modifies activity of said acid-sensing ion channels of the DEG/ENaC family. (patentsencyclopedia.com)
- This gene encodes a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. (genecards.org)
- This article is from PLoS ONE, volume 9.AbstractAcid-sensing ion channels Asic are ligand-gated ion channels in the Degenerin-Epithelial Na+ channel Deg-ENaC family. (duhnnae.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)
- 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)
ASIC16
- In mammals, acid-sensing ion channels (ASIC) are encoded by five genes that produce ASIC protein subunits: ASIC1, ASIC2, ASIC3, ASIC4, and ASIC5. (wikipedia.org)
- The chicken acid-sensing ion channel ASIC1 has been crystallized as a homotrimer. (sigmaaldrich.com)
- We selected most pathways ASIC1 participated on our site, such as Inflammatory mediator regulation of TRP channels, which may be useful for your reference. (creativebiomart.net)
- ASIC1 has several biochemical functions, for example, acid-sensing ion channel activity, ion gated channel activity, ligand-gated sodium channel activity. (creativebiomart.net)
- 7, which is sufficient to activate ASIC1 a and ASIC3 channels in vitro. (diff.org)
- The neuronally expressed, proton-gated acid-sensing ion channel-1 (ASIC1) is permeable to Na+ and Ca2+, and excessive accumulation of these ions is associated with axonal degeneration. (ox.ac.uk)
ASIC22
- We have thus identified domains of ASIC2 that are crucial to channel function and may be important for the function of other members of the ASIC family. (aspetjournals.org)
- The outcome of this study is meaningful since it identified a new cell membrane merging mechanism of the Acid-sensing Ion Channel, and furthermore is significant that it proposed a research direction for a new understanding of the activity control mechanism of various ion channels among subunits including ASIC2, ASIC2b and many other subunits. (scienmag.com)
Cation channels2
- Waldmann, R. & Lazdunski, M. H + -gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels. (nature.com)
- Acid-sensing ion channels are cation channels activated by external protons and play roles in nociception, synaptic transmission, and the physiopathology of ischemic stroke. (sigmaaldrich.com)
Proteins12
- The atomic structure of acid-sensing ion channel 1 illustrates the complex trimeric architecture of these proteins. (nih.gov)
- Several metrics were collected to facilitate the analyses of the expected relationships: maximum confidence score transferred, maximum confidence score transferred from the Experiments channel in STRING, the varieties from which the relationships were transferred, and the eggNOG non-supervised orthologous organizations (NOGs) the proteins belong to. (monossabios.com)
- Collectively, these findings describe a novel mechanism of nociceptor sensitization and firmly establish reducing agents, as well as Zn 2+ , Zn 2+ -chelating amino acids, and Zn 2+ -chelating proteins as endogenous modulators of Ca v 3.2 and nociceptor excitability. (jneurosci.org)
- In 2009 the use of styrene maleic acid co-polymers (SMA) for the effective extraction/solubilisation of membrane proteins was first reported [ 10 ]. (portlandpress.com)
- Some synapses include specialized proteins that 'sense' acidity. (scientificamerican.com)
- The Iowa study shows that genetically modified mice lacking these acid-sensing proteins have a greatly reduced capacity to show either instinctive or learned fear. (scientificamerican.com)
- Ion channels are proteins composed of amino acids, the blueprint of which is coded by the genes. (innovations-report.com)
- Generally, G protein-gated ion channels are specific ion channels located in the plasma membrane of cells that are directly activated by a family of associated proteins. (wikipedia.org)
- A class known as metabotropic glutamate receptors play a large role in indirect ion channel activation by G proteins. (wikipedia.org)
- They only directly activate these ion channels using effector proteins or the G protein subunits themselves (see picture). (wikipedia.org)
- Unlike most effectors, not all G protein-gated ion channels have their activity mediated by Gα of their corresponding G proteins. (wikipedia.org)
- These domains on the N-and C-terminal ends which interact with the G proteins contain certain residues which are critical for the proper activation of the GIRK channel. (wikipedia.org)
Inhibition4
- We show that inhibition of these channels using a "double-knot" spider venom peptide massively attenuates brain damage after stroke and improves behavioral outcomes, even when the peptide is administered 8 h after stroke onset. (pnas.org)
- In this study, we examined the detailed zinc inhibition of ASIC1b currents and specific amino acid(s) involved in the inhibition. (nih.gov)
- 2018) Inhibition of acid-sensing ion channels by diminazene and APETx2 evoke partial and highly variable antihyperalgesia in a rat model of inflammatory pain. (guidetopharmacology.org)
- The inhibition of potassium channels by peptides from animal venoms is a subject of broad interest for its physiological and therapeutic applications [ 1 ]. (mdpi.com)
Neuronal4
- Certain peptides even lead to clinical development and venom-based drugs, such as ziconotide, which is an inhibitor of neuronal voltage-gated calcium channels isolated from Conus magus , designed for patients with intra-ctable pain who fail to respond to other drugs [ 57 , 66 ]. (intechopen.com)
- 1997) BNaC1 and BNaC2 Constitute a New Family of Human Neuronal Sodium Channels Related to Degenerins and Epithelial Sodium Channels. (springer.com)
- Members of the ASIC family of acid-sensing ion channels are abundant in various regions of the brain and mediate neuronal synaptic function. (sciencemag.org)
- A family of proton-gated sodium channels that are primarily expressed in neuronal tissue. (rush.edu)
Pharmacology1
- 1. Baron A, Lingueglia E. (2015) Pharmacology of acid-sensing ion channels - Physiological and therapeutical perspectives. (guidetopharmacology.org)
Sensory7
- Acid-sensing ion channels are broadly distributed in the nervous system where they contribute to the sensory processes. (nih.gov)
- 1998) A Sensory Neuron-Specific, Proton-Gated Ion Channel. (springer.com)
- 2002) Proinflammatory Mediators, Stimulators of Sensory Neuron Excitability Via the Expression of Acid-Sensing Ion Channels. (springer.com)
- Lingueglia E (2007) Acid-sensing ion channels in sensory perception. (springer.com)
- 5. Mamet J, Baron A, Lazdunski M, Voilley N. (2002) Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels. (guidetopharmacology.org)
- These channels are sensitive to changes in pH and are expressed throughout the central and peripheral nervous systems-including brain, spinal cord, and sensory ganglia. (tdl.org)
- The researchers therefore investigated the function of this ion channel in naked mole-rat and in mouse sensory nerves to determine whether there is a difference between the two species in the function of this ion channel. (innovations-report.com)
Subunits13
- Three of these protein subunits assemble to form the ASIC, which can combine into both homotrimeric and heterotrimeric channels typically found in both the central nervous system and peripheral nervous system. (wikipedia.org)
- However, the gating and mechanics of each acid-sensing ion channel is determined by the combination of ASIC subunits that form its structure. (wikipedia.org)
- 6, and the combination of different subunits can produce properties different from those of homomeric channels. (diff.org)
- pH Dependency and desensitization kinetics of heterologously expressed combinations of acid-sensing ion channel subunits. (semanticscholar.org)
- This acidic pocket contains several pairs of acidic amino acids, is situated at the interface between two subunits, and is considered one of the ASIC pH sensors. (biomedcentral.com)
- These subunits form functional ion channels as dimers or heteropolymers, and differing channels vary in activation conditions, ion selectivity, kinetics, and distributions. (biomedcentral.com)
- The research team identified through animal experiments that there is a different cell membrane merging mechanism between subunits of the Acid-sensing Ion Channel. (scienmag.com)
- A trimer of subunits comprises the channel ( 4 ), which can be composed of homologous or heterologous subunits. (pnas.org)
- These three altered protein subunits lead to profound impairment or blockage of the naked mole-rat ion channel by acid. (innovations-report.com)
- Four G protein gated inwardly-rectifying potassium (GIRK) channel subunits have been identified in mammals: GIRK1, GIRK2, GIRK3, and GIRK4. (wikipedia.org)
- The GIRK subunits come together to form GIRK ion channels. (wikipedia.org)
- Because of their similarity, the GIRK channel subunits can come together easily to form heteromultimers (a protein with two or more different polypeptide chains). (wikipedia.org)
- Though GIRK3 subunits are found in the CNS, their role in forming functional ion channels is still unknown. (wikipedia.org)
ASIC32
- Sustained currents through ASIC3 ion channels at the modest pH changes that occur during myocardial ischemia. (semanticscholar.org)
- Homozygous Asic3 (amiloride-sensitive cation channel 3) targeted mutation mice display alterations in normal and pain-associated cutaneous mechanosensitivity and inflammatory pain sensation, visual loss associated with night blindness, and age-induced hearing loss. (jax.org)
Blockers7
- However, the sustained depolarization was not blocked by amiloride but was eliminated by removal of K + from the pipette solution which reduced significantly intracellular K + . This sustained depolarization was partially blocked by the TASK channels blockers anandamide (from 14.9±1.6 mV to 9.3±2.2 mV at pH 6.0, n=5) and quinidine (from 27.5±2.2 mV to 11.3±2.3 mV at pH 6.0, n=3). (ahajournals.org)
- Monoamine NMDA receptor channel blockers inhibit and potentiate native and recombinant proton-gated ion channels. (nih.gov)
- Common binding site for externally and internally applied AMPA receptor channel blockers. (nih.gov)
- Organic blockers escape from trapping in the AMPA receptor channels by leaking into the cytoplasm. (nih.gov)
- Effects of ionotropic glutamate receptor channel blockers on the development of pentylenetetrazol kindling in mice. (nih.gov)
- A subclass of sodium channel blockers that are specific for ACID-SENSING SODIUM CHANNELS. (nih.gov)
- Dentists already use sodium ion channel blockers in the form of local anesthetics, but these target all sodium ion channels they come into contact with, not just the Nav1.7 ion channel. (innovations-report.com)
Currents4
- Cation channel that gives rise to very low constitutive currents in the absence of activation. (uniprot.org)
- a phenomenon that adds to the functional diversity of acid-mediated currents. (aspetjournals.org)
- In whole-cell voltage-clamp recording, ASIC currents were evoked by brief local application of pH 6.0 external solution in the presence of TRPV1 channel blocker AMG9810. (chinaphar.com)
- The acid- or proton-activated Cl − (PAC) currents are present in a wide range of mammalian cells ( 2 ). (sciencemag.org)
Superfamily1
- This gene belongs to the superfamily of acid-sensing ion channels, which are proton-gated, amiloride-sensitive sodium channels. (genecards.org)
Potentiates acid-sen1
- Histamine selectively potentiates acid-sensing ion channel 1a. (nih.gov)
Transmembrane4
- ASIC4 has several biochemical functions, for example, ion channel activity, sodium channel activity, sodium ion transmembrane transporter activity. (creativebiomart.net)
- A disulphide-rich "tumb" domain is between the acidic residues and the transmembrane pore: it may couple the binding of protons to the opening of the ion channel. (diff.org)
- The protein, called PAC for proton-activated channel, has two predicted transmembrane domains and is unlike any previously identified channel. (sciencemag.org)
- These ion channels are transmembrane ion channels with selectivity filters and a G protein binding site. (wikipedia.org)
Inhibitor1
- proteolytic cleavage of human acid-sensing ion channel 1 [ PMID: 20601429 ] and the regulation of the matriptase-prostasin cell surface proteolytic cascade by hepatocyte growth factor activator inhibitor-1 during epidermal differentiation [ PMID: 20696767 ]. (ebi.ac.uk)
Protein9
- The intracellular amino-carboxyl termini domains are vital to the channel's intracellular protein interactions and modulations, ion permeability, and gating. (wikipedia.org)
- TMD2 is primarily involved with lining of the lumen within the pore and inactivation gate of the channel, where as TMD1 holds the protein within the cell's lipid bilayer. (wikipedia.org)
- 2002) Protein Kinase C Stimulates the Acid-Sensing Ion Channel ASIC2a Via the PDZ Domain-Containing Protein PICK1. (springer.com)
- In the twelve years since styrene maleic acid (SMA) was first used to extract and purify a membrane protein within a native lipid bilayer, this technological breakthrough has provided insight into the structural and functional details of protein-lipid interactions. (portlandpress.com)
- Several of the experiments described in the Iowa paper showed that inhaling elevated concentrations of carbon dioxide triggered strong fear reactions in normal mice, and that some of these fear reactions required the presence of the acid-sensing protein in the amygdala. (scientificamerican.com)
- used an unbiased RNA interference screen to identify the channel protein that allows such proton-activated ion conductance. (sciencemag.org)
- G protein-gated ion channels are associated with a specific type of G protein-coupled receptor. (wikipedia.org)
- The GPCRs associated with G protein-gated ion channels are not involved in signal transduction pathways. (wikipedia.org)
- These domains interact directly with the βγ-complex of the G protein, leading to activation of the K+ channel. (wikipedia.org)
Inhibits acid-sen1
- Potent neuroprotection after stroke afforded by a double-knot spider toxin that inhibits acid-sensing ion channel 1a. (cipps.org.au)
Amiloride-sensitive cation1
- This mutant mouse line contains a transgene that consists of a hemagglutnin-tagged mouse Accn3 (amiloride-sensitive cation channel 3)cDNA driven by the rat Syn1 (synapsin1) promoter. (jax.org)
Peptides2
- Peptides inhibitors of acid-sensing ion channels. (qxmd.com)
- Dual signaling of Wamide myoinhibitory peptides through a peptide-gated channel and a GPCR in Platynereis. (ukaachen.de)
Mechanisms9
- To explore structure-function, gating mechanisms and tissue localization of many ion channels, animal venom toxins were important pharmacological tools in the ion channel field [ 28 ]. (intechopen.com)
- This review describes findings that provide new insights into the molecular mechanisms that control the function of these channels. (nih.gov)
- However, despite considerable research efforts, the mechanisms of ion acquisition and identity of the transporters involved in ion uptake in fresh water are still not fully understood. (biologists.org)
- Modulation of acid-sensing ion channels: molecular mechanisms and therapeutic potential. (semanticscholar.org)
- Discovery of the ASIC crystal structure provided insight into inherent mechanisms of channel depolarization, inactivation, and modulation. (biomedcentral.com)
- Professor Suh's research team detected the cell membrane merging mechanisms that modulate the activity of the Acid-sensing Ion Channel at the molecular level, and it is this discovery and identification of the new cell membrane merging mechanism of the Acid-sensing Ion Channel that had remained unknown until now. (scienmag.com)
- Mechanisms of the blockade of glutamate channel receptors: significance for structural and physiological investigations. (nih.gov)
- However, the molecular mechanisms underlying the functions of T-channels in nociceptors are poorly understood. (jneurosci.org)
- However, the molecular mechanisms of the cellular response to acid are not fully understood. (sciencemag.org)
Physiological5
- The combination of the structural and physiological data indicates that Mamba1 prefers to bind hASIC1a in a closed state and reduces the proton sensitivity of the channel, representing a closed-state trapping mechanism. (elifesciences.org)
- Venom toxins in the exploration of molecular, physiological and pathophysiological functions of acid-sensing ion channels. (semanticscholar.org)
- Exposure of cells to acidic conditions outside the cell activates chloride-conducting channels that influence physiological and pathological processes. (sciencemag.org)
- Identification of the channel should advance studies of its physiological roles, which range from tissue injury after stroke to adaptation of Tibetan natives to a high-altitude environment. (sciencemag.org)
- The wide expression of PAC suggests a broad role for this conserved Cl − channel family in physiological and pathological processes associated with acidic pH. (sciencemag.org)
Inhibitors2
- Diarylamidines: high potency inhibitors of acid-sensing ion channels. (nih.gov)
- MacDonald, John F. / Diarylamidines : High potency inhibitors of acid-sensing ion channels . (elsevier.com)
Peptide4
- Sea anemones are a rich source of two classes of peptide toxins, sodium channel toxins and potassium channel toxins, which have been or will be useful tools for studying the structure and function of specific ion channels. (springer.com)
- Of the three classes of toxins, both sodium and potassium channel peptide toxins have been useful tools for studying the structure and function of ion channels, because of their high affinity to the specific channel. (springer.com)
- 1975 ), more than 50 sodium channel peptide toxins have been isolated and/or cloned from various species of sea anemones. (springer.com)
- 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)
Functional3
- ASIC2b is non-functional on its own but modulates channel activity when participating in heteromultimers and ASIC4 has no known function. (wikipedia.org)
- Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system. (semanticscholar.org)
- Kühn, F.J.P. Ehrlich, W. Barth, D. Kühn, C. Lückhoff, A. Functional importance of NUDT9H domain and N-terminal ADPR-binding pocket in two species variants of vertebrate TRPM2 channels. (ukaachen.de)
Selectivity6
- The activated channel exhibits selectivity for sodium, and is inhibited by amiloride. (uniprot.org)
- At pH 7.25 the pore is approximately 10 Å in diameter, whereas at pH 5.5 the pore is largely hydrophobic and elliptical in cross-section with dimensions of approximately 5 by 7 Å, consistent with a barrier mechanism for ion selectivity. (rcsb.org)
- Here, we explored the basis for ion selectivity by incorporating unnatural amino acids into the channel, engineering channel stoichiometry and performing free energy simulations. (elifesciences.org)
- Thus, the molecular determinants of ion selectivity and in turn the basis for excitatory function in this family of ligand-gated ion channel remains an open question. (elifesciences.org)
- Both approaches support the conclusion that other parts of the pore contribute more markedly to ion selectivity than the GAS belt. (elifesciences.org)
- BDS-I and II, which show selectivity for Kv3.4 channels and APETx1, which inhibits human ether-a-go-go -related gene potassium channels. (springer.com)
Modulation3
- These residues form an acidic pocket that express electrostatic potentials that are responsible for pH-dependency in channel activation and modulation. (wikipedia.org)
- Muscarinic M1 modulation of acid-sensing ion channels. (qxmd.com)
- Collectively, our data further support a role for Ca v 3.2 channels in peripheral nociception and identify a novel mechanism for Ca v 3.2 modulation that underlies nociceptor sensitization. (jneurosci.org)
20171
- AUGUSTA, Ga. (Sept. 5, 2017) - 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 report. (eurekalert.org)
Gene3
- Gene Ontology (GO) annotations related to this gene include ion channel activity and voltage-gated sodium channel activity . (genecards.org)
- Our group combines recombinant DNA technology, electrophysiology, in vivo imaging, gene targeting and behavioural approaches to explore the channels, receptors, transcription factors and regulatory pathways that control nociceptor excitability. (ucl.ac.uk)
- In a number of mammals the structure of the gene for the Nav1.7 ion channel has been decoded. (innovations-report.com)
Peripheral1
- The overall goal of the experiments proposed in this application is to shed light on the role played by lactic acid in evoking the exercise pressor reflex in both health and simulated peripheral artery disease. (elsevier.com)
Expression6
- Price, M. P., Snyder, P. M. & Welsh, M. J. Cloning and expression of a novel human brain Na + channel. (nature.com)
- Acid-sensing Ion Channels Activation and Hypoxia Upregulate Homer1a Expression. (medworm.com)
- 2001) Nonsteroid Anti-Inflammatory Drugs Inhibit Both the Activity and the Inflammation-Induced Expression of Acid-Sensing Ion Channels in Nociceptors. (springer.com)
- 1. Voilley N, de Weille J, Mamet J, Lazdunski M. (2001) Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. (guidetopharmacology.org)
- Their expression within areas of interest in the brain in migraine, such as the hypothalamus and PAG, their demonstrated involvement in preclinical models of meningeal afferent signaling, and their role in cortical spreading depression (the electrophysiological correlate of migraine aura), has enhanced research interest into these channels as potential therapeutic targets in migraine. (tdl.org)
- Vol 9: Restrictive Expression of Acid-Sensing Ion Channel 5 Asic5 in Unipolar Brush Cells of the Vestibulocerebellum. (duhnnae.com)
20161
- Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking of ASIC2b via Heteromeric Assembly', Scientific Reports 2016. (scienmag.com)
Nociceptors2
Modulate4
- These observations led to the hypothesis that ASIC s, and possibly other acid-activated receptors, have a critical role in nociception, but how ASIC s transduce or modulate painful stimuli has not been established yet. (diff.org)
- In particular, this invention relates to pharmaceutical compositions, dietary supplements and methods of treatment which modulate the acid-sensing ion channel (ASIC) for treatment of Central Nervous System (CNS) disorders such as seizures and strokes through synaptic plasticity, treatment of cognitive disorders, and for memory enhancement. (patentsencyclopedia.com)
- Heteromeric channel assembly seems to modulate. (genecards.org)
- Ligands of histamine receptors modulate acid-sensing ion channels. (nih.gov)
Synaptic2
- These channels have been implicated in synaptic transmission, pain perception as well as mechanoperception. (genecards.org)
- We now know that they contribute to synaptic transmission at excitatory synapses as well as to sensing metabolic acidosis and nociception. (oxfordhandbooks.com)
MeSH1
- Acid Sensing Ion Channels" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (rush.edu)
Amino acid2
- Amino acid sequences of soidum channel toxins from sea anemones. (springer.com)
- In the NaV1.7 ion channel of the naked mole-rat, three amino acid building blocks are different from those in all other mammals. (innovations-report.com)
Activates2
- The precipitous drop in brain pH resulting from stroke activates acid-sensing ion channel 1a. (pnas.org)
- In body tissues, CO2 is converted into acid, which continuously activates pain sensors. (innovations-report.com)
Activate4
- However, it remains fairly inconclusive of which particular residues interact with protons to activate the channel. (wikipedia.org)
- These high acid levels in the tissue activate the pain sensors. (innovations-report.com)
- This is also the case when in the nerve cells of the naked mole-rats other ion channels are activated by acid stimuli that would normally activate pain receptors. (innovations-report.com)
- A troubled lung also becomes acidic, which can activate this acid sensing ion channel. (eurekalert.org)
Intracellular1
- The molecular mechanism of pH sensing by chemoreceptors is not clear, although it had been proposed to be mediated by a drop in intracellular pH of carotid body glomus cells, which inhibits a K + current. (ahajournals.org)
Human Acid-sensing Ion1
- Proteolytic cleavage of human acid-sensing ion channel 1 by the serine protease matriptase. (ebi.ac.uk)
Chicken acid-sensing ion1
- Divalent cation and chloride ion sites of chicken acid sensing ion channel 1a elucidated by x-ray crystallography. (ohsu.edu)
Pore2
- Finally, we identify by molecular docking a binding site in the ion pore that we confirm by site-directed mutagenesis. (aspetjournals.org)
- Each channel consists of domains which span the plasma membrane, forming the K+-selective pore region through which the K+ ions will flow. (wikipedia.org)
Receptors3
- Acid-sensitive ion channels and receptors. (semanticscholar.org)
- However, naked mole-rats are an exception: they have an altered ion channel in their pain receptors that is inactivated by acid and makes the animals insensitive to this type of pain. (innovations-report.com)
- Identification of aurintricarboxylic acid as a potent allosteric antagonist of P2X1 and P2X3 receptors. (ukaachen.de)
ASIC Channel1
- It averaged 40.7±15.7 pA (n=5) at pH 5.0 and was blocked by the ASIC channel blocker amiloride (200 μm) to 2.5±1.6 pA. (ahajournals.org)
Acidic1
- Although the threshold to elicit I Cl,H is relatively low, ~pH 5.5 at room temperature (RT), the channels become activated under less acidic conditions of ~pH 6.0 at 37°C ( 3 , 4 ). (sciencemag.org)
Therapeutic4
- Venoms of species like spiders, sea anemones and snakes have been found to target ion channels with highly therapeutic potentials as drug candidates [ 17 , 38 ]. (intechopen.com)
- Acid-sensing ion channels: advances, questions and therapeutic opportunities. (semanticscholar.org)
- The findings are expected to have a significant impact on further studies focusing on the development of therapeutic agents that control pain by providing a more precise understanding of the operational mechanism of the 'Acid-sensing Ion Channel' that plays a pivotal role in transmitting pain signals. (scienmag.com)
- Sodium Channels in Pain and Cancer: New Therapeutic Opportunities. (ucl.ac.uk)
Nociception1
- 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)