ArticleNeuron2018
The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel.
Article in Neuron, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 99 citations in OpenAlex.
- Pacemaking in the lymphatic system.The Journal of physiology · 2026Review
- TMEM16A channel signalling microdomains in the regulation of vascular function.The Journal of physiology · 2026Review
- Conformational changes upon pore blocker removal reveal conductive states of TMEM16A.bioRxiv : the preprint server for biology · 2026Article
- Alpha-ketoglutarate supplementation ameliorates castor oil-induced diarrhea in mice: in silico and in vivo insights.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · 2026Article
- Simulation-based survey of TMEM16 family reveals that robust lipid scrambling requires an open groove.eLife · 2025Article
- 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
- Simulation-based survey of TMEM16 family reveals that robust lipid scrambling requires an open groove.bioRxiv : the preprint server for biology · 2025Article
- Wide-ranging cellular functions of ion channels and lipid scramblases in the structurally related TMC, TMEM16 and TMEM63 families.Nature structural & molecular biology · 2025Review
- Tamsulosin ameliorates bone loss by inhibiting the release of ClProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Distinct modulation of calcium-activated chloride channel TMEM16A by drug-binding sites.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Predicting Mutational Effects on CaJournal of the American Chemical Society · 2024Article
- Structure of mechanically activated ion channel OSCA2.3 reveals mobile elements in the transmembrane domain.Structure (London, England : 1993) · 2024Article
- Mechanistic basis of ligand efficacy in the calcium-activated chloride channel TMEM16A.The EMBO journal · 2023Article
- Article
- KCNE1 does not shift TMEM16A from a CaPflugers Archiv : European journal of physiology · 2023Article
- Establishment of a CaCC-based Cell Model and Method for High-throughput Screening of M3 Receptor Drugs.Cell biochemistry and biophysics · 2023Article
- Gating and anion selectivity are reciprocally regulated in TMEM16A (ANO1).The Journal of general physiology · 2022Article
- Mechanical gating of the auditory transduction channel TMC1 involves the fourth and sixth transmembrane helices.Science advances · 2022Article
- Inhibition mechanism of the chloride channel TMEM16A by the pore blocker 1PBC.Nature communications · 2022Article
- TMEM16 scramblases thin the membrane to enable lipid scrambling.Nature communications · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Calcium-activated chloride channels (CaCCs) formed by TMEM16A or TMEM16B are broadly expressed in the nervous system, smooth muscles, exocrine glands, and other tissues. With two calcium-binding sites and a pore within each monomer, the dimeric CaCC exhibits voltage-dependent calcium sensitivity. Channel activity also depends on the identity of permeant anions. To understand how CaCC regulates neuronal signaling and how CaCC is, in turn, modulated by neuronal activity, we examined the molecular basis of CaCC gating. Here, we report that voltage modulation of TMEM16A-CaCC involves voltage-dependent occupancy of calcium- and anion-binding site(s) within the membrane electric field as well as a voltage-dependent conformational change intrinsic to the channel protein. These gating modalities all critically depend on the sixth transmembrane segment.
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Registered trials
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.