Explaining calcium-dependent gating of anoctamin-1 chloride channels requires a revised topology.

ABSTRACT:

Rationale

Ca2+ -activated Cl channels play pivotal roles in the cardiovascular system. They regulate vascular smooth muscle tone and participate in cardiac action potential repolarization in some species. Ca2+ -activated Cl channels were recently discovered to be encoded by members of the anoctamin (Ano, also called Tmem16) superfamily, but the mechanisms of Ano1 gating by Ca2+ remain enigmatic.

Objective

The objective was to identify regions of Ano1 involved in channel gating by Ca2+.

Methods and results

The Ca2+ sensitivity of Ano1 was estimated from rates of current activation, and deactivation in excised patches rapidly switched between zero and high Ca2+ on the cytoplasmic side. Mutation of glutamates E702 and E705 dramatically altered Ca2+ sensitivity. E702 and

SUBMITTER: Yu K 

PROVIDER: S-EPMC3558997 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature