TRPC1-5-5-5 heteromer as a sodium sensor

초록

The classical TRPC channel is a key Ca2+-permeable cation channel in mammalian cells. TRPC5, a non-selective cation channel, plays a vital role in membrane depolarization and calcium influx, forming both homotetramers and heterotetramers with TRPC1. In this study, we confirmed the optimal co-expression of TRPC1-5 and TRPC5-5 concatemers to investigate the unique natural characteristics of TRPC1/5. Recent findings indicate that Gi2QL plays a role in activating both TRPC1-5 and TRPC5-5, where Gi2QL activation results in ideal concatemeric current. Moreover, an increase in internal calcium concentration exclusively activates the TRPC5-5 homomeric concatemer, while increased internal sodium concentration selectively activates the TRPC1-5-5-5 concatemer in co-expression. This sodium sensitivity aligns with a putative Na+-binding site at the TRPC1-5 interface revealed by structural modeling. Our results reveal the subunit composition of TRPC1/5 channels and clarify the molecular mechanisms driving their activation.

키워드