• They include proteins from several structurally different families: chloride channel accessory (CLCA), bestrophin (BEST), and calcium-dependent chloride channel anoctamin (ANO or TMEM16) channels ANO1 is highly expressed in human gastrointestinal interstitial cells of Cajal, which are proteins which serve as intestinal pacemakers for peristalsis. (wikipedia.org)
  • We hypothesize that disruption of vectorial Cl transport by 5-HT may be critical in determining the alveolar flooding and abnormalities in intestinal Cl secretion through stimulation of anoctamin 1(ANO1) Cl channel. (cancertreatmentsresearch.com)
  • Anoctamin 1 (ANO1) encoded Ca2+-activated Cl- channels were found to be involved in tumorigenesis. (cancertreatmentsresearch.com)
  • Recessive mutations in the putative calcium-activated chloride channel anoctamin 5 cause proximal LGMD2L and distal MMD3 muscular dystrophies. (bvsalud.org)
  • Transmembrane protein 16A (TMEM16A) channels are recently discovered membrane proteins that functions as a calcium activated chloride channel (CaCC). (elsevierpure.com)
  • TMEM16A is a calcium activated chloride channel (CaCC) which opens in response to increases in calcium inside lung cells. (cff.org)
  • The potentiator compounds are small-molecule drugs that make the CaCC channel more sensitive to small increases in calcium within the cells, thereby activating the channel more frequently and allowing more chloride to flow across the cell membrane. (cff.org)
  • Elevated 5-HT activates luminal ANO1 CaCC in the intestinal and lung epithelium by a mechanism that appears to involve the rise of [Ca 2+ ] i . (cancertreatmentsresearch.com)
  • TMEM16A (ANO1) functions as a calcium-activated chloride channel (CaCC). (csnpharm.cn)
  • Endovion is a blocker of both VRAC and CaCC with IC50 value around 400nM for blocking swelling-activated anion currents in HEK293 cells. (csnpharm.cn)
  • Eact is an activator of TMEM16A calcium-activated chloride channel (CaCC) with EC50 of 3 μM. (csnpharm.cn)
  • CLCA proteins are thought to mediate calcium-activated chloride currents and are obviously involved in many other cellular functions, including mucus production,andhydration of mucus membranes of thenose, trachea and lungrespiratoryas well as theintestinal tractintestineandmodulation ofinnate immune responses. (fu-berlin.de)
  • Liu X , Grove JC , Hirano AA, Brecha NC , Barnes S . Dopamine D1 receptor modulation of calcium channel currents in horizontal cells of mouse retina. (neurotree.org)
  • Apamin-sensitive calcium-activated potassium currents in rabbit ventricles with chronic myocardial infarction. (harvard.edu)
  • Cerebellar ataxia by enhanced Ca(V)2.1 currents is alleviated by Ca2+-dependent K+-channel activators in Cacna1a(S218L) mutant mice. (harvard.edu)
  • We next confirmed ANO1-currents activated by 5-HT in the Caco-2 cells by patch-clamp measurements of whole-cell current. (cancertreatmentsresearch.com)
  • These results indicated that 5-HT evoked calcium-activated Cl currents through ANO1 channels. (cancertreatmentsresearch.com)
  • We next confirmed the presence of ANO1 currents activated by 5-HT in Calu-3 cells by the Ussing chamber experiments. (cancertreatmentsresearch.com)
  • T16Ainh-A01, an aminophenylthiazole, is a potent transmembrane protein 16A (TMEM16A) inhibitor, inhibiting TMEM16A-mediated chloride currents with an IC50 value of ~1 µM. (csnpharm.cn)
  • The whole-cell voltage clamp method ( 6 ) was chosen to measure swelling-induced chloride currents in isolated NIH 3T3 fibroblasts, colon carcinoma (CaCo) cells, and H9 cells, a human T cell lymphoma cell line (ATCC HTB 176). (biomedcentral.com)
  • Ca2+) (in) CaCCs that are known to occur in humans include: Accessories: CLCA1, CLCA2, CLCA3, and CLCA4 Anoctamins: ANO1 and ANO2 (potentially others) Bestrophins: BEST1, BEST2, BEST3, and BEST4 Voltage-gated ion channel Ion channel The anoctamins are only expressed in eukaryotes, with 10 members in vertebrates. (wikipedia.org)
  • CLCA1 (calcium-activated chloride channel regulator 1) was the most upregulated gene transcript (>100-fold) in all exposed mouse lungs versus controls, followed closely by SLC26A4, another transcript involved in Cl- conductance. (cdc.gov)
  • Crofelemer, a U.S. Food and Drug Administration-approved Cl- channel inhibitor, reduced MDI exposure induction of airway eosinophilia, mucus, CLCA1, and other asthma-associated gene transcripts. (cdc.gov)
  • Furthermore, in a study based on a molecular approach, Woodruff and colleagues discovered that IL-13 can stimulate the expression of chloride channel, calcium-activated, family member 1 (CLCA1), periostin, serine peptidase inhibitor, clade B (ovalbumin), and serpin family B member 2 (serpinB2), all of which are overexpressed in asthmatic individuals (8). (ees2010prague.org)
  • In addition to their role as chloride channels some CLCA proteins function as adhesion molecules and may also have roles as tumour suppressors. (wikipedia.org)
  • While the specific function of this protein is not well understood, it belongs to a family of proteins, called anoctamins, that act as chloride channels. (medlineplus.gov)
  • One of the major aims of Dr. Ebihara's research project are to obtain a more detailed understanding of the biophysical properties of cloned lens gap junctional proteins and to localize the molecular determinants of permeability and gating of the gap junctional channels. (rosalindfranklin.edu)
  • Ion channels are pore-forming proteins that allow the flow of ions across membranes, either plasma membranes, or the membranes of intracellular organelles [ 4 ]. (guidetoimmunopharmacology.org)
  • Activation mechanism of the calcium-activated chloride channel TMEM16A revealed by cryo-EM" (PDF). (wikipedia.org)
  • Unlike other potentiators under development, the potential medicines target TMEM16A, an alternative chloride channel to CFTR. (cff.org)
  • Shikonin is an inhibitor of TMEM16A chloride channel with IC50 of 6.5 μM, it's a natural product isolated and purified from the roots of Lithosperraum erythrorhizon Sieb. (csnpharm.cn)
  • In this HOT paper , the Schmitzer group at the Université de Montréal are particularly interested in the transport of chloride ions in epithelial cells through calcium activated ion channels. (rsc.org)
  • They hope to mediate the concentrations of both calcium and chloride ions using synthetic ionophores. (rsc.org)
  • Building on their research into imidazolium amphiphiles , they have developed a benzimidazolium-based compound that increases chloride flux in a variety of lipid bilayer systems, and increases bacterial cell wall permeability to calcium ions. (rsc.org)
  • Cell membrane glycoproteins that form channels to selectively pass chloride ions. (nih.gov)
  • The most prominent feature of Best1 is its significant permeability to glutamate and GABA in addition to chloride ions because glutamate and GABA are important transmitters in the brain. (en-journal.org)
  • R(+)-IAA-94 is a potent indanyloxyacetic acid blocker of epithelial chloride channels. (csnpharm.cn)
  • We investigated the swelling-induced chloride current in fibroblasts, which we demonstrated is closely related or identical to a cloned epithelial chloride channel, I Cln . (biomedcentral.com)
  • Potassium channels whose activation is dependent on intracellular calcium concentrations. (harvard.edu)
  • In exocrine acinar cells regulation of intracellular calcium plays a pivotal role in controlling fluid and protein secretion. (rochester.edu)
  • Exposure of cells to neurotransmitters and hormones results in a rapid elevation of intracellular calcium. (rochester.edu)
  • Many ion channels (such as most Na, K, Ca and some Cl channels) are gated by voltage but others (such as certain K and Cl channels, TRP channels, ryanodine receptors and IP 3 receptors) are relatively voltage-insensitive and are gated by second messengers and other intracellular and/or extracellular mediators. (guidetoimmunopharmacology.org)
  • Unlike other channels, opening of the pore is due to the repositioning of tethered pore-lining helices within a surrounding protein shell that dramatically widens a neck of the pore through a concertina of amino acid rearrangements. (elifesciences.org)
  • This compound will hopefully inspire new drugs to treat cystic fibrosis, which is caused by mutation of a chloride-ion channel known as the cystic fibrosis transmembrane conductance regulator protein (CFTR). (rsc.org)
  • ANO1 is a transmembrane protein that functions as a calcium-activated chloride channel. (cancertreatmentsresearch.com)
  • Although there are many remaining uncertainties, this review highlights the idea that Best1 is a multifunctional protein, functioning as an anion channel with unique properties as well as a key regulator of various important brain functions. (en-journal.org)
  • Bcl-xL acts as an inhibitor of IPR channels, thereby antagonizing Ca-driven apoptosis. (rochester.edu)
  • NS1652 is a reversible anion conductance inhibitor, blocks chloride channel, with an IC50 of 1.6 μM in human and mouse red blood cells. (csnpharm.cn)
  • NPPB can act as a blocker of the chloride channel with IC50 of 100 nM-100 µM and inhibitor of cyclooxygenase (IC50 = 8 µM). (csnpharm.cn)
  • IAA-94 is an indanyloxyacetic acid (IAA) inhibitor of chloride channels that binds channels in bovine kidney cortex microsomes with a Ki value of 1 µM. (csnpharm.cn)
  • Studies to date indicate that endothelial cells express glycine-activated chloride channels, which promote hyperpolarization of the endothelial plasma membrane. (nih.gov)
  • Correction to: Rare variants in ANO1, encoding a calcium-activated chloride channel, predispose to moyamoya disease. (medscape.com)
  • Because calcium-activated chloride current in human intestinal epithelia remains controversial, we examined the localization of ANO1 in the human terminal ileum and colonic tissue using confocal microscopy. (cancertreatmentsresearch.com)
  • Previous studies suggest the effect of ANO1 gene amplification on tumorigenic proliferation is exerted through its channel function. (cancertreatmentsresearch.com)
  • Cellular mechanisms underlying the inhibitory effect of flufenamic acid on chloride secretion in human intestinal epithelial cells. (harvard.edu)
  • Inhibition of intestinal chloride secretion by piperine as a cellular basis for the anti-secretory effect of black peppers. (harvard.edu)
  • Since macrophages express glycine-activated chloride channels that suppress production of oxidants and cytokines, glycine may also oppose atherogenesis by influencing intimal macrophage function. (nih.gov)
  • In addition to chemokines and alternatively activated monocytes/macrophages, the data suggest a crucial role for Cl- channels in diisocyanate asthma pathology and as a possible target for intervention. (cdc.gov)
  • Researchers suggest that the mutations may affect the way cells process calcium, an important mineral in bone development and growth. (medlineplus.gov)
  • Restoring neuronal chloride extrusion reverses cognitive decline linked to Alzheimer's disease mutations. (medscape.com)
  • Bestrophin-1 (Best1) is a calcium-activated anion channel identified from retinal pigment epithelium where human mutations are associated with Best's macular degeneration. (en-journal.org)
  • Biological Membrane Ion Channels , edn. (edu.au)
  • This reflects the fact that endothelial hyperpolarization promotes calcium influx, activating the endothelial isoform of nitric oxide synthase, while also down-regulating the activity of the membrane-bound NADPH oxidase, chief endothelial source of superoxide. (nih.gov)
  • The vast majority of this transportation occurs through ion channels or pores in the cell membrane. (rsc.org)
  • Sun X , Hirano AA, Brecha NC , Barnes S . Calcium-activated BKCa channels govern dynamic membrane depolarizations of horizontal cells in rodent retina. (neurotree.org)
  • It is also transient receptor potential vanilloid 1 (TRPV1) channel activator (EC50 = 11.6 μM). (csnpharm.cn)
  • Potassium Channels, Calcium-Activated" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
  • This graph shows the total number of publications written about "Potassium Channels, Calcium-Activated" by people in Harvard Catalyst Profiles by year, and whether "Potassium Channels, Calcium-Activated" was a major or minor topic of these publication. (harvard.edu)
  • Below are the most recent publications written about "Potassium Channels, Calcium-Activated" by people in Profiles. (harvard.edu)
  • Discovery of Novel Activators of Large-Conductance Calcium-Activated Potassium Channels for the Treatment of Cerebellar Ataxia. (harvard.edu)
  • Surprisingly, however, whereas metazoan bestrophin channels are anion-selective and activated by Ca 2+ , KpBest is cation-selective and does not contain the Ca 2+ sensor region (the 'Ca 2+ clasp') that is conserved amongst metazoan organisms. (elifesciences.org)
  • VRAC, volume-regulated anion channels. (silverchair.com)
  • Here we show that the release of ATP induced by hypotonic stress (HTS) in bovine aortic endothelial cells (BAECs) occurs through volume-regulated anion channels (VRAC). (silverchair.com)
  • The mechanism for this calcium activation is unclear. (medlineplus.gov)
  • Absorption of strontium from the gastrointestinal tract shares a common mechanism with absorption of calcium. (cdc.gov)
  • Targeted Deletion of Vesicular GABA Transporter from Retinal Horizontal Cells Eliminates Feedback Modulation of Photoreceptor Calcium Channels. (neurotree.org)
  • Farrell SR , Rankin DR, Brecha NC , Barnes S . Somatostatin receptor subtype 4 modulates L-type calcium channels via Gβγ and PKC signaling in rat retinal ganglion cells. (neurotree.org)
  • Farrell SR , Sargoy A , Brecha NC , Barnes S . Modulation of voltage-gated Ca2+ channels in rat retinal ganglion cells by gabapentin. (neurotree.org)
  • Selamectin is a potent nematocide used for the treatment of parasites, which selectively binds to parasite glutamate-gated chloride ion channels and disrupts neurotransmission. (csnpharm.cn)
  • Tmc1 and Tmc2 (TC#s 1.A.17.4.6 and 1.A.17.4.1, respectively) may play a role in hearing and are required for normal function of cochlear hair cells, possibly as Ca2+ channels or Ca2+ channel subunits (see also family TC# 1.A.82). (wikipedia.org)
  • Subsequent studies showed activation of calcium channels in response to pulsed electromagnetic frequencies in plants, animals, and human cells. (news-medical.net)
  • Tong JJ, Acharya P, Ebihara L. Calcium-Activated Chloride Channels in Newly Differentiating Mouse Lens Fiber Cells and Their Role in Volume Regulation. (rosalindfranklin.edu)
  • If such channels are expressed by endothelial cells lining conduit arteries, glycine is likely to have anti-atherogenic activity. (nih.gov)
  • Researchers in Canada have developed the first benzimidazolium-based synthetic ion channel and shown that it can cause damage to bacterial cells walls. (rsc.org)
  • Case Report on: Very Early Afterdepolarizations in HiPSC-Cardiomyocytes-An Artifact by Big Conductance Calcium Activated Potassium Current (Ibk,Ca). Cells. (harvard.edu)
  • A further project relates to the organization and regulation of calcium release sites in exocrine cells. (rochester.edu)
  • Electrophysiological, fluorescence optical, and volume measurements were made to determine the effect of nucleoside analogs on the swelling-dependent chloride current (I Cl ) in NIH 3T3 fibroblasts and in human T cell lymphoma (H9) cells and the cAMP-dependent chloride current in CaCo cells. (biomedcentral.com)
  • AZT and acyclovir block the swelling-dependent chloride current and the chloride flux in fibroblasts, and the regulatory volume decrease (RVD) and I Cl in H9 cells. (biomedcentral.com)
  • For electrical measurements in H9 cells, glass cover slips were coated with a 0.25% collagen solution (type I). All experiments were carried out at room temperature (20-22°C). Bath and pipette solutions were chosen to enable chloride current measurements. (biomedcentral.com)
  • Tetrodotoxin exerts its effects by blocking voltage-activated sodium channels, terminating nerve conduction and muscle action potentials, leading to progressive paralysis and, in extreme cases, to death from respiratory failure. (cdc.gov)
  • Fluxametamide is an insecticide with wide spectrum, acts as an antagonist of GABA- and glutamate-gated chloride channels, with IC50 of 1.95 nM and 225 nM for M. domestica GABACls and GluCls. (csnpharm.cn)
  • Fluralaner (INN) is a systemic insecticide and acaricide Fluralaner through potent blockage of GABA and L-glutamate gated chloride channels. (csnpharm.cn)
  • Mice lacking both channels lack hair cell mechanosensory potentials. (wikipedia.org)
  • Effects of calcium-activated potassium channel modulators on afterhyperpolarizing potentials in identified motor and mechanosensory neurons of the medicinal leech. (harvard.edu)
  • Bound ATP occludes the channel at moderate positive potentials, but permeates into the cytosol at more depolarized potentials. (silverchair.com)
  • In rats, supplemental glycine exerts anti-inflammatory and anti-angiogenic effects attributed to chloride channel activation. (nih.gov)
  • His interests and those of his research groups have included exploring the mechanisms of ion permeation and selectivity in ion channels, the relationship between the molecular structure and the physiological function of channels, such as those of the inhibitory neurotransmitter receptor glycine channel and the olfactory cyclic nucleotide-gated channel, and investigating the factors that determine their ion permeation, selectivity and conductance. (edu.au)
  • Ca(2+)-activated K(+) channel-3.1 blocker TRAM-34 attenuates airway remodeling and eosinophilia in a murine asthma model. (harvard.edu)
  • Niflumic acid, a Ca2+-activated Cl- channel blocker, is an analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis. (csnpharm.cn)
  • This phenomenon could be described with a "permeating blocker model," in which ATP binds with an affinity of 1.0 ± 0.5 mM at 0 mV to a site at an electrical distance of 0.41 inside the channel. (silverchair.com)
  • Partly because bestrophin channels have no sequence or structural similarity to other ion channels, the molecular mechanisms underlying gating are unknown. (elifesciences.org)
  • 1. Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R. (1998) The structure of the potassium channel: molecular basis of K+ conduction and selectivity. (guidetoimmunopharmacology.org)
  • 3. Dutzler R, Campbell EB, Cadene M, Chait BT, MacKinnon R. (2002) X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity. (guidetoimmunopharmacology.org)
  • 4. Hille B. (1986) Ionic channels: molecular pores of excitable membranes. (guidetoimmunopharmacology.org)
  • 2005) Overview of molecular relationships in the voltage-gated ion channel superfamily. (guidetoimmunopharmacology.org)
  • The increased flow of chloride is expected to help hydrate mucus within the airways, making it easier to expel and decreasing the likelihood of infections. (cff.org)
  • mCLCA3 Does Not Contribute to Calcium-Activated Chloride Conductance in Murine Airways. (fu-berlin.de)
  • One of the first studies to elucidate how the pulsed electromagnetic frequencies could affect human health showed that low-intensity pulsed electromagnetic frequencies could be blocked using drugs that block voltage-gated calcium channels. (news-medical.net)
  • The Porcine Chloride Channel Calcium-Activated Family Member pCLCA4a Mirrors Lung Expression of the Human hCLCA4. (fu-berlin.de)
  • The reactions believed to be catalyzed by channels of the Ca-ClC family are: Cl− (out) ⇌ Cl− (in) and Cations (e.g. (wikipedia.org)
  • Members of this family function as chloride anion channels. (modellab.cn)