title: Divalent cations modulate TMEM16A calcium-activated chloride channels by a common mechanism.
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.
authors.affiliation: Institute of Biophysics, School of Sciences, Hebei University of Technology, 5340 Xiping Road, Tianjin, 300401, People's Republic of China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Yuan
authors.forename: Chongsen
authors.initials: C
authors.lastname: Gao
authors.forename: Yafei
authors.initials: Y
authors.lastname: Chen
authors.forename: Mengwen
authors.initials: M
authors.lastname: Jia
authors.forename: Jinpeng
authors.initials: J
authors.lastname: Geng
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhan
authors.forename: Linda M
authors.initials: LM
authors.lastname: Boland
authors.forename: Hailong
authors.initials: H
authors.lastname: An
mesh_terms: D000075369:Anoctamin-1; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism*; D002460:Cell Line; D018118:Chloride Channels / Q000378:metabolism*; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D008564:Membrane Potentials; D009363:Neoplasm Proteins / Q000378:metabolism*; D009532:Nickel / Q000378:metabolism; D013324:Strontium / Q000378:metabolism; D014162:Transfection; D015032:Zinc / Q000378:metabolism
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D002413:Cations, Divalent; D018118:Chloride Channels; D009363:Neoplasm Proteins; D009532:Nickel; D015032:Zinc; D002118:Calcium; D013324:Strontium