ArticleAmerican journal of physiology. Cell physiology2016
Influence of intracellular Ca2+ and alternative splicing on the pharmacological profile of ANO1 channels.
Article in American journal of physiology. Cell physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- ER morphological analysis associated with interstitial cells of Cajal and smooth muscle cells in the murine stomach.Cell and tissue research · 2025Article
- Molecular mechanisms of activation and regulation of ANO1-Encoded CaChannels (Austin, Tex.) · 2021Review
- The CaActa pharmaceutica Sinica. B · 2021Review
- Allosteric modulation of alternatively spliced CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Development of a QPatch-Automated Electrophysiology Assay for Identifying TMEM16A Small-Molecule Inhibitors.Assay and drug development technologies · 2020Article
- Calcium-Activated Chloride Channel ANO1/TMEM16A: Regulation of Expression and Signaling.Frontiers in physiology · 2020Review
- NaFrontiers in physiology · 2020Article
- Molecular mechanism of TMEM16A regulation: role of CaMKII and PP1/PP2A.American journal of physiology. Cell physiology · 2019Article
- Na-K-2Cl Cotransporter and Store-Operated CaBiophysical journal · 2019Article
- Molecular mechanisms of caffeine-mediated intestinal epithelial ion transports.British journal of pharmacology · 2019Article
- Differential sensitivity of gastric and small intestinal muscles to inducible knockdown of anoctamin 1 and the effects on gastrointestinal motility.The Journal of physiology · 2019Article
- Calcium-Activated Chloride Channels in Newly Differentiating Mouse Lens Fiber Cells and Their Role in Volume Regulation.Investigative ophthalmology & visual science · 2019Article
- Ano1 mediates pressure-sensitive contraction frequency changes in mouse lymphatic collecting vessels.The Journal of general physiology · 2019Article
- Tonic inhibition of murine proximal colon is due to nitrergic suppression of CaScientific reports · 2019Article
- Spontaneous Electrical Activity and Rhythmicity in Gastrointestinal Smooth Muscles.Advances in experimental medicine and biology · 2019Review
- SOCE mediated by STIM and Orai is essential for pacemaker activity in the interstitial cells of Cajal in the gastrointestinal tract.Science signaling · 2018Article
- The effects of mitochondrial inhibitors on CaCell calcium · 2018Article
- Functional comparison of anoctamin 1 antagonists on human uterine smooth muscle contractility and excitability.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2018Article
- Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A (TMEM16A).Journal of medicinal chemistry · 2017Article
- Cellular distribution and function of ion channels involved in transport processes in rat tracheal epithelium.Physiological reports · 2017Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Anoctamin-1 (ANO1) is a Ca(2+)-activated Cl(-) channel expressed in many types of cells. Splice variants of ANO1 have been shown to influence the biophysical properties of conductance. It has been suggested that several new antagonists of ANO1 with relatively high affinity and selectivity might be useful for experimental and, potentially, therapeutic purposes. We investigated the effects of intracellular Ca(2+) concentration ([Ca(2+)]i) at 100-1,000 nM, a concentration range that might be achieved in cells during physiological activation of ANO1 channels, on blockade of ANO1 channels expressed in HEK-293 cells. Whole cell and excised patch configurations of the patch-clamp technique were used to perform tests on a variety of naturally occurring splice variants of ANO1. Blockade of ANO1 currents with aminophenylthiazole (T16Ainh-A01) was highly dependent on [Ca(2+)]i Increasing [Ca(2+)]i reduced the potency of this blocker. Similar Ca(2+)-dependent effects were also observed with benzbromarone. Experiments on excised, inside-out patches showed that the diminished potency of the blockers caused by intracellular Ca(2+) might involve a competitive interaction for a common binding site or repulsion of the blocking drugs by electrostatic forces at the cytoplasmic surface of the channels. The degree of interaction between the channel blockers and [Ca(2+)]i depends on the splice variant expressed. These experiments demonstrate that the efficacy of ANO1 antagonists depends on [Ca(2+)]i, suggesting a need for caution when ANO1 blockers are used to determine the role of ANO1 in physiological functions and in their use as therapeutic agents.
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