Dual action of the Gα_q-PLCβ-PI(4,5)P₂ 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)P₂. 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)P₂, which inhibits activity of TRPC1/4 and 1/5 channels.