Dual action of the Gα(q)-PLCβ-PI(4,5)P(2) pathway on TRPC1/4 and TRPC1/5 heterotetramers

The transient receptor potential canonical (TRPC) 1 channel is widely distributed in mammalian cells and is involved in many physiological processes. TRPC1 is primarily considered a regulatory subunit that forms heterotetrameric channels with either TRPC4 or TRPC5 subunits. Here, we suggest that the regulation of TRPC1/4 and TRPC1/5 heterotetrameric channels by the Gα(q)-PLCβ pathway is self-limited and dynamically mediated by Gα(q) and PI(4,5)P(2). We provide evidence indicating that Gα(q) protein directly interacts with either TRPC4 or TRPC5 of the heterotetrameric channels to permit activation. Simultaneously, Gα(q)-coupled PLCβ activation leads to the breakdown of PI(4,5)P(2), which inhibits activity of TRPC1/4 and 1/5 channels.