ArticleThe Journal of biological chemistry2009
Regulation of TMEM16A chloride channel properties by alternative splicing.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 1 of them a synthesis that pooled it.
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Who cites it
135 citing papers in PubMed, 1 synthesis or guideline pooled it, 204 citations in OpenAlex.
- ANO1: More Than Just Calcium-Activated Chloride Channel in Cancer.Frontiers in oncology · 2022Pooled it
- TMEM16A channel signalling microdomains in the regulation of vascular function.The Journal of physiology · 2026Review
- Evaluating the molecular function of zebrafish Anoctamin 1a.microPublication biology · 2025Article
- Missense variants in ANO4 cause sporadic encephalopathic or familial epilepsy with evidence for a dominant-negative effect.American journal of human genetics · 2024Article
- 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
- Vasodilators activate the anion channel TMEM16A in endothelial cells to reduce blood pressure.Science signaling · 2023Article
- 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
- Intracellular Loop in the Brain Isoforms of Anoctamin 2 Channels Regulates Calcium-dependent Activation.Experimental neurobiology · 2023Article
- Transcriptomic analysis of lung development in wildtype and CFTRFunctional & integrative genomics · 2023Article
- Phosphatidylinositol 4,5-Bisphosphate and Cholesterol Regulators of the Calcium-Activated Chloride Channels TMEM16A and TMEM16B.Advances in experimental medicine and biology · 2023Article
- Polymodal Control of TMEM16x Channels and Scramblases.International journal of molecular sciences · 2022Review
- Molecular mechanisms of activation and regulation of ANO1-Encoded CaChannels (Austin, Tex.) · 2021Review
- Review
- Functional expression of TMEM16A in taste bud cells.The Journal of physiology · 2021Article
- Gender-Dependent Phenotype in Polycystic Kidney Disease Is Determined by Differential Intracellular CaInternational journal of molecular sciences · 2021Article
- The CaActa pharmaceutica Sinica. B · 2021Review
- Differential Regulation of CaInternational journal of molecular sciences · 2021Article
- Divalent Cation Modulation of Ion Permeation in TMEM16 Proteins.International journal of molecular sciences · 2021Article
75 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Expression of TMEM16A protein is associated with the activity of Ca(2+)-activated Cl(-) channels. TMEM16A primary transcript undergoes alternative splicing. thus resulting in the generation of multiple isoforms. We have determined the pattern of splicing and assessed the functional properties of the corresponding TMEM16A variants. We found three alternative exons, 6b, 13, and 15, coding for segments of 22, 4, and 26 amino acids, respectively, which are differently spliced in human organs. By patch clamp experiments on transfected cells, we found that skipping of exon 6b changes the Ca(2+) sensitivity by nearly 4-fold, resulting in Cl(-) currents requiring lower Ca(2+) concentrations to be activated. At the membrane potential of 80 mV, the apparent half-effective concentration decreases from 350 to 90 nm when the segment corresponding to exon 6b is excluded. Skipping of exon 13 instead strongly reduces the characteristic time-dependent activation observed for Ca(2+)-activated Cl(-) channels at positive membrane potentials. This effect was also obtained by deleting only the second pair of amino acids corresponding to exon 13. Alternative splicing appears as an important mechanism to regulate the voltage and Ca(2+) dependence of the TMEM16A-dependent Cl(-) channels in a tissue-specific manner.
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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.