ArticlePflugers Archiv : European journal of physiology2015
Characterization of the effects of Cl⁻ channel modulators on TMEM16A and bestrophin-1 Ca²⁺ activated Cl⁻ channels.
Article in Pflugers Archiv : European journal of physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 98 citations in OpenAlex.
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- Triggered Calcium Lightning Programs Cochlear Development.Exploration (Beijing, China) · 2026Article
- CLN3 mediates chloride efflux from lysosomes.Neuron · 2026Article
- Pleiotropic Effects of the NSAID Fenamates on Chloride Channels: Opportunity for Ion Channelopathies?Pharmacology research & perspectives · 2025Review
- Vitexicarpin suppresses colorectal and non-small cell lung cancer via selective inhibition of Anoctamin 1.Frontiers in pharmacology · 2025Article
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- The Tmem16a chloride channel is required for mucin maturation after secretion from goblet-like cells in the Xenopus tropicalis tadpole skin.Scientific reports · 2024Article
- Glutamate-releasing BEST1 channel is a new target for neuroprotection against ischemic stroke with wide time window.Acta pharmaceutica Sinica. B · 2023Article
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- Pharmacological modulation of chloride channels as a therapeutic strategy for neurological disorders.Frontiers in physiology · 2023Review
- Anoctamins and Calcium Signalling: An Obstacle to EGFR Targeted Therapy in Glioblastoma?Cancers · 2022Review
- Chloride Channels and Transporters: Roles beyond Classical Cellular Homeostatic pH or Ion Balance in Cancers.Cancers · 2022Review
- Polymodal Control of TMEM16x Channels and Scramblases.International journal of molecular sciences · 2022Review
- Structure and Function of the Bestrophin family of calcium-activated chloride channels.Channels (Austin, Tex.) · 2021Review
- The diverse roles of TMEM16A CaJournal of advanced research · 2021Review
- Emerging Modulators of TMEM16A and Their Therapeutic Potential.The Journal of membrane biology · 2021Review
- P2X7 Receptors and TMEM16 Channels Are Functionally Coupled with Implications for Macropore Formation and Current Facilitation.International journal of molecular sciences · 2021Article
- The CaActa pharmaceutica Sinica. B · 2021Review
- PAR-2-activated secretion by airway gland serous cells: role for CFTR and inhibition byAmerican journal of physiology. Lung cellular and molecular physiology · 2021Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The Ca(2+) activated Cl(-) channels (CaCCs) play a multitude of important physiological functions. A number of candidate proteins have been proposed to form CaCC, but only two families, the bestrophins and the TMEM16 proteins, recapitulate the properties of native CaCC in expression systems. Studies of endogenous CaCCs are hindered by the lack of specific pharmacology as most Cl(-) channel modulators lack selectivity and a systematic comparison of the effects of these modulators on TMEM16A and bestrophin is missing. In the present study, we studied seven Cl(-) channel inhibitors: niflumic acid (NFA), NPPB, flufenamic acid (FFA), DIDS, tannic acid, CaCCinh-A01 and T16Ainh-A01 for their effects on TMEM16A and bestrophin-1 (Best1) stably expressed in CHO (Chinese hamster ovary) cells using patch clamp technique. Among seven inhibitors studied, NFA showed highest selectivity for TMEM16A (IC50 of 7.40 ± 0.95 μM) over Best1 (IC50 of 102.19 ± 15.05 μM). In contrast, DIDS displayed a reverse selectivity inhibiting Best1 with IC50 of 3.93 ± 0.73 μM and TMEM16A with IC50 of 548.86 ± 25.57 μM. CaCCinh-A01 was the most efficacious blocker for both TMEM16A and Best1 channels. T16Ainh-A01 partially inhibited TMEM16A currents but had no effect on Best1 currents. Tannic acid, NPPB and FFA had variable intermediate effects. Potentiation of channel activity by some of these modulators and the effects on TMEM16A deactivation kinetics were also described. Characterization of Cl(-) channel modulators for their effects on TMEM16A and Best1 will facilitate future studies of native CaCCs.
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