Activation of the Ano1 (TMEM16A) chloride channel by calcium is not mediated by calmodulin.

ABSTRACT: The Ca(2+)-activated Cl channel anoctamin-1 (Ano1; Tmem16A) plays a variety of physiological roles, including epithelial fluid secretion. Ano1 is activated by increases in intracellular Ca(2+), but there is uncertainty whether Ca(2+) binds directly to Ano1 or whether phosphorylation or additional Ca(2+)-binding subunits like calmodulin (CaM) are required. Here we show that CaM is not necessary for activation of Ano1 by Ca(2+) for the following reasons. (a) Exogenous CaM has no effect on Ano1 currents in inside-out excised patches. (b) Overexpression of Ca(2+)-insensitive mutants of CaM have no effect on Ano1 currents, whereas they eliminate the current mediated by the small-conductance Ca(2+)-activated K(+) (SK2) channel. (c) Ano1 does not coimmunoprecipitate with CaM, whereas SK2 does. Fu

SUBMITTER: Yu K 

PROVIDER: S-EPMC4001774 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature