Differential PI(4,5)P 2 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 Gα q -PLC pathway. Since phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ) maintains TRPC4 and TRPC5 channel function, the Gα q -PLC pathway inhibits channel activity by depleting PI(4,5)P 2 . Here we investigated the difference in PI(4,5)P 2 sensitivity between homomeric and heteromeric TRPC channels. First, by using a Danio rerio voltage-sensing phosphatase (DrVSP), we show that PI(4,5)P 2 dephosphorylation robustly inhibits TRPC4α, TRPC4β, and TRPC5 homotetramer currents and also TRPC1/4α, TRPC1/4β, and TRPC1/5 heterotetramer currents. Secondly, sensitivity of channels to PI(4,5)P 2 dephosphorylation was suggested through the usage of FRET in combination with patch clamping. The sensitivity increased in the sequence TRPC4β < TRPC4α