TRPC1 and TRPC5 form a novel cation channel in mammalian brain

TRP proteins are cation channels responding to receptor-dependent activatio n of phospholipase C. Mammalian (TRPC) channels can form hetero-oligomeric channels in vitro, but native TRPC channel complexes have not been identifi ed to date. We demonstrate here that TRPC1 and TRPC5 are subunits of a hete romeric neuronal channel. Both TRPC proteins have overlapping distributions in the hippocampus. Coexpression of TRPC1 and TRPC5 in HEK293 cells result ed in a novel nonselective cation channel with a voltage dependence similar to NMDA receptor channels, but unlike that of any reported TRPC channel. T RPC1/TRPC5 heteromers were activated by G(q)-coupled receptors but not by d epletion of intracellular Ca2+ stores. In contrast to the more common view of the TRP family as comprising store-operated channels, we propose that ma ny TRPC heteromers form diverse receptor-regulated nonselective cation chan nels in the mammalian brain.