Intracellular calcium activates TRPM2 and its alternative spliced isoforms.

ABSTRACT: Melastatin-related transient receptor potential channel 2 (TRPM2) is a Ca(2+)-permeable, nonselective cation channel that is involved in oxidative stress-induced cell death and inflammation processes. Although TRPM2 can be activated by ADP-ribose (ADPR) in vitro, it was unknown how TRPM2 is gated in vivo. Moreover, several alternative spliced isoforms of TRPM2 identified recently are insensitive to ADPR, and their gating mechanisms remain unclear. Here, we report that intracellular Ca(2+) ([Ca(2+)](i)) can activate TRPM2 as well as its spliced isoforms. We demonstrate that TRPM2 mutants with disrupted ADPR-binding sites can be activated readily by [Ca(2+)](i), indicating that [Ca(2+)](i) gating of TRPM2 is independent of ADPR. The mechanism by which [Ca(2+)](i) activates TRPM2 is via a cal

SUBMITTER: Du J 

PROVIDER: S-EPMC2678461 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature