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Divalent Cations Modulate TMEM16A Calcium-Activated Chloride Channels by a Common Mechanism

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Abstract

The gating of Ca2+-activated Cl− channels is controlled by a complex interplay among [Ca2+]i, membrane potential and permeant anions. Besides Ca2+, Ba2+ also can activate both TMEM16A and TMEM16B. This study reports the effects of several divalent cations as regulators of TMEM16A channels stably expressed in HEK293T cells. Among the divalent cations that activate TMEM16A, Ca2+ is most effective, followed by Sr2+ and Ni2+, which have similar affinity, while Mg2+ is ineffective. Zn2+ does not activate TMEM16A but inhibits the Ca2+-activated chloride currents. Maximally effective concentrations of Sr2+ and Ni2+ occluded activation of the TMEM16A current by Ca2+, which suggests that Ca2+, Sr2+ and Ni2+ all regulate the channel by the same mechanism.

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Abbreviations

CaCCs:

Ca2+-activated Cl− currents

[Ca2+]i :

Intracellular calcium concentration

Vm :

Membrane potential

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Acknowledgments

This work was supported by 11247010 from NSFC and C2012202079 from Hebei NSFC to H. A., 11175055 from NSFC to Y. Z., 31270882 from NSFC and 2013CB531302 from National Basic Research Program to H. Z., and 30900267 from NSFC to Z. Z.

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Authors and Affiliations

  1. Institute of Biophysics, School of Sciences, Hebei University of Technology, 5340 Xiping Road, Tianjin, 300401, People’s Republic of China

    Hongbo Yuan, Chongsen Gao, Yafei Chen, Mengwen Jia, Jinpeng Geng, Yong Zhan & Hailong An

  2. Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of Pharmacology and Toxicology for New Drug, Hebei Province, Department of Pharmacology, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China

    Hailin Zhang

  3. Department of Biology, University of Richmond, Richmond, VA, 23114, USA

    Linda M. Boland

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  1. Hongbo Yuan
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  2. Chongsen Gao
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  7. Yong Zhan
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Correspondence to Yong Zhan, Linda M. Boland or Hailong An.

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Yuan, H., Gao, C., Chen, Y. et al. Divalent Cations Modulate TMEM16A Calcium-Activated Chloride Channels by a Common Mechanism. J Membrane Biol 246, 893–902 (2013). https://doi.org/10.1007/s00232-013-9589-9

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