ArticleProceedings of the National Academy of Sciences of the United States of America2011
Voltage- and calcium-dependent gating of TMEM16A/Ano1 chloride channels are physically coupled by the first intracellular loop.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers.
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Who cites it
150 citing papers in PubMed, 218 citations in OpenAlex.
- An All-Optical Approach to Probe Chloride Transport with a Bright ChlorON.bioRxiv : the preprint server for biology · 2026Article
- Synaptic activity controls local exposure of an 'eat-me' signal via ANO3-ITPR1 signaling.bioRxiv : the preprint server for biology · 2026Article
- Review of the clinical electrooculogram - Part 1: Mechanism of the Light-Rise.Documenta ophthalmologica. Advances in ophthalmology · 2026Review
- TMEM16A channel signalling microdomains in the regulation of vascular function.The Journal of physiology · 2026Review
- ER stress-induced ITPR1/ANO1 signaling drives trigeminal neuropathic pain through calcium-dependent neuronal hyperexcitability.The journal of headache and pain · 2025Article
- [Transmembrane protein 16A--a new target for the treatment of airway inflammatory diseases].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025Review
- Calcium-activated chloride channel TMEM16A opens via pi-helical transition in transmembrane segment 4.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Anoctamin-1 is a core component of a mechanosensory anion channel complex in C. elegans.Nature communications · 2025Article
- The emerging role of anoctamin-1 in cardiac and cerebrovascular diseases.Frontiers in cardiovascular medicine · 2025Review
- Evaluating the molecular function of zebrafish Anoctamin 1a.microPublication biology · 2025Article
- Mechanism of action and therapeutic value of anoctamin-1 in gastrointestinal cancers.Frontiers in immunology · 2025Review
- The Tmem16a chloride channel is required for mucin maturation after secretion from goblet-like cells in the Xenopus tropicalis tadpole skin.Scientific reports · 2024Article
- Niclosamide potentiates TMEM16A and induces vasoconstriction.The Journal of general physiology · 2024Article
- Missense variants in ANO4 cause sporadic encephalopathic or familial epilepsy with evidence for a dominant-negative effect.American journal of human genetics · 2024Article
- CaInternational journal of molecular sciences · 2024Review
- The role of anoctamin 1 in liver disease.Journal of cellular and molecular medicine · 2024Review
- Structure and Function of Calcium-Activated Chloride Channels and Phospholipid Scramblases in the TMEM16 Family.Handbook of experimental pharmacology · 2024Review
- Impaired amygdala astrocytic signaling worsens neuropathic pain-associated neuronal functions and behaviors.Frontiers in pharmacology · 2024Article
- Rare variants in ANO1, encoding a calcium-activated chloride channel, predispose to moyamoya disease.Brain : a journal of neurology · 2023Article
- KCNE1 does not shift TMEM16A from a CaPflugers Archiv : European journal of physiology · 2023Article
90 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Ca(2+)-activated Cl(-) channels (CaCCs) are exceptionally well adapted to subserve diverse physiological roles, from epithelial fluid transport to sensory transduction, because their gating is cooperatively controlled by the interplay between ionotropic and metabotropic signals. A molecular understanding of the dual regulation of CaCCs by voltage and Ca(2+) has recently become possible with the discovery that Ano1 (TMEM16a) is an essential subunit of CaCCs. Ano1 can be gated by Ca(2+) or by voltage in the absence of Ca(2+), but Ca(2+)- and voltage-dependent gating are very closely coupled. Here we identify a region in the first intracellular loop that is crucial for both Ca(2+) and voltage sensing. Deleting (448)EAVK in the first intracellular loop dramatically decreases apparent Ca(2+) affinity. In contrast, mutating the adjacent amino acids (444)EEEE abolishes intrinsic voltage dependence without altering the apparent Ca(2+)affinity. Voltage-dependent gating of Ano1 measured in the presence of intracellular Ca(2+) was facilitated by anions with high permeability or by an increase in [Cl(-)](e). Our data show that the transition between closed and open states is governed by Ca(2+) in a voltage-dependent manner and suggest that anions allosterically modulate Ca(2+)-binding affinity. This mechanism provides a unified explanation of CaCC channel gating by voltage and ligand that has long been enigmatic.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.