title: A novel biophysical model on calcium and voltage dual dependent gating of calcium-activated chloride channel.
abstract: Ca(2+)-activated Cl(-) channels (CaCCs) are anion-selective channels and involved in physiological processes such as electrolyte/fluid secretion, smooth muscle excitability, and olfactory perception which critically depend on the Ca(2+) and voltage dual-dependent gating of channels. However, how the Ca(2+) and voltage regulate the gating of CaCCs still unclear. In this work, the authors constructed a biophysical model to illustrate the dual-dependent gating of CaCCs. For validation, we applied our model on both native CaCCs and exogenous TMEM16A which is thought to be the molecular basis of CaCCs. Our data show that the native CaCCs may share universal gating mechanism. We confirmed the assumption that by binding with the channel, Ca(2+) decreases the energy-barrier to open the channel, but not changes the voltage-sensitivity. For TMEM16A, our model indicates that the exogenous channels show different Ca(2+) dependent gating mechanism from the native ones. These results advance the understanding of intracellular Ca(2+) and membrane potential regulation in CaCCs, and shed new light on its function in aspect of physiology and pharmacology.
authors.affiliation: School of Sciences, Hebei University of Technology, Tianjin 300130, China.
authors.forename: Suhua
authors.initials: S
authors.lastname: Zhang
authors.affiliation: School of Sciences, Hebei University of Technology, Tianjin 300130, China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Sciences, Hebei University of Technology, Tianjin 300130, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: An
authors.affiliation: School of Sciences, Hebei University of Technology, Tianjin 300130, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: School of Sciences, Hebei University of Technology, Tianjin 300130, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Sciences, Hebei University of Technology, Tianjin 300130, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Pang
authors.affiliation: School of Sciences, Hebei University of Technology, Tianjin 300130, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ji
authors.affiliation: School of Sciences, Hebei University of Technology, Tianjin 300130, China. Electronic address: zhany@hebut.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhan
mesh_terms: D000075369:Anoctamin-1; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D018118:Chloride Channels / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D018118:Chloride Channels; D009363:Neoplasm Proteins; D002118:Calcium
keywords: Biophysical model; Ca(2+)-activated Cl(−) channels; Calcium and voltage dual dependence; Gating mechanism; Steady-state open probability