Activation of Ca(2+) -activated Cl(-) channel ANO1 by localized Ca(2+) signals.
Ca(2+)-activated chloride channels (CaCCs) regulate numerous physiological processes including epithelial transport, smooth muscle contraction and sensory processing. Anoctamin-1 (ANO1, TMEM16A) is a principal CaCC subunit in many cell types, yet our understanding of the mechanisms of ANO1 activation and regulation are only beginning to emerge. Ca(2+) sensitivity of ANO1 is rather low and at negative membrane potentials the channel requires several micromoles of intracellular Ca(2+) for activation. However, global Ca(2+) levels in cells rarely reach such levels and, therefore, there must be mechanisms that focus intracellular Ca(2+) transients towards the ANO1 channels. Recent findings indeed indicate that ANO1 channels often co-localize with sources of intracellular Ca(2+) signals. Interestingly, it appears that in many cell types ANO1 is particularly tightly coupled to the Ca(2+) release sites of the intracellular Ca(2+) stores. Such preferential coupling may represent a general mechanism of ANO1 activation in native tissues.
School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK.
Xin
X
Jin
School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK.
Sihab
S
Shah
Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
Xiaona
X
Du
Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
Hailin
H
Zhang
School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK.|Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
Nikita
N
Gamper
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism* / Q000502:physiology
D018118:Chloride Channels; D002118:Calcium