Mechanism of allosteric activation of TMEM16A/ANO1 channels by a commonly used chloride channel blocker.

ABSTRACT:

Background and purpose

Calcium-activated chloride channels (CaCCs) play varied physiological roles and constitute potential therapeutic targets for conditions such as asthma and hypertension. TMEM16A encodes a CaCC. CaCC pharmacology is restricted to compounds with relatively low potency and poorly defined selectivity. Anthracene-9-carboxylic acid (A9C), an inhibitor of various chloride channel types, exhibits complex effects on native CaCCs and cloned TMEM16A channels providing both activation and inhibition. The mechanisms underlying these effects are not fully defined.

Experimental approach

Patch-clamp electrophysiology in conjunction with concentration jump experiments was employed to define the mode of interaction of A9C with TMEM16A channels.

Key results

In the

SUBMITTER: Ta CM 

PROVIDER: S-EPMC4728427 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature