Differential PI(4,5)P2 sensitivities of TRPC4, C5 homomeric and TRPC1/4, C1/5 heteromeric channels.

ABSTRACT: Transient receptor potential canonical (TRPC) 4 and TRPC5 channels are modulated by the G?q-PLC pathway. Since phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) maintains TRPC4 and TRPC5 channel function, the G?q-PLC pathway inhibits channel activity by depleting PI(4,5)P2. Here we investigated the difference in PI(4,5)P2 sensitivity between homomeric and heteromeric TRPC channels. First, by using a Danio rerio voltage-sensing phosphatase (DrVSP), we show that PI(4,5)P2 dephosphorylation robustly inhibits TRPC4?, TRPC4?, and TRPC5 homotetramer currents and also TRPC1/4?, TRPC1/4?, and TRPC1/5 heterotetramer currents. Secondly, sensitivity of channels to PI(4,5)P2 dephosphorylation was suggested through the usage of FRET in combination with patch clamping. The sensitivity increased in the sequence TRPC4??

SUBMITTER: Ko J 

PROVIDER: S-EPMC6372716 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature