The disordered C-terminal tail of TRPA1 is required for calmodulin binding and desensitization

Abstract

TRPA1 is a non-selective cation channel that has been Identified as a potential drug target for persistent pain since it is required for thermal and mechanical hypersensitivity. While TRPA1 channel gating by direct agonists has been resolved, the pathways that control TRPA1 channel regulation are not well characterized. Increases in intracellular calcium control both TRPA1 potentiation and desensitization, but the mechanisms that govern these processes are poorly understood. Our research shows that calmodulin is required for TRPA1 channel desensitization, and TRPA1 lacks intrinsic channel desensitization capability unlike other ion channels.