Physiological functions and regulation of TRPC channels

Abstract

The TRP-canonical (TRPC) subfamily, which consists of seven members (TRPC1-TRPC7), are Ca2+-permeable cation channels that are activated in response to receptor-mediated PIP2 hydrolysis via store-dependent and storeindependent mechanisms. These channels are involved in a variety of physiological functions in different cell types and tissues. Of these, TRPC6 has been linked to a channelopathy resulting in human disease. Two key players of the store-dependent regulatory pathway, STIM1 and Orai1, interact with some TRPC channels to gate and regulate channel activity. The Ca2+ influx mediated by TRPC channels generates distinct intracellular Ca2+ signals that regulate downstream signaling events and consequent cell functions. This requires localization of TRPC channels in specific plasma membrane microdomains and precise regulation of channel function which is coordinated by various scaffolding, trafficking, and regulatory proteins. © 2014 Springer International Publishing Switzerland.