TRPC1 and TRPC5 Form a Novel Cation Channel in Mammalian Brain

• Published in: Neuron (Cambridge, Mass.) Vol. 29; no. 3; pp. 645 - 655
• Main Authors: Strübing, Carsten, Krapivinsky, Grigory, Krapivinsky, Luba, Clapham, David E
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2001
• Subjects: Animals; Axons - chemistry; Brain Chemistry; Calcium - analysis; Calcium Channels - analysis; Calcium Channels - chemistry; Calcium Channels - genetics; Cation Transport Proteins; Cations; Cell Line; Dendrites - chemistry; Electric Conductivity; Embryo, Mammalian; Gene Expression; Hippocampus - chemistry; Humans; Ion Channels - chemistry; Kidney; Macromolecular Substances; Neurons - chemistry; Neurons - ultrastructure; Rats; Receptors, N-Methyl-D-Aspartate - physiology; Transfection; Trp protein; TRPC Cation Channels
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(01)00240-9

TRP proteins are cation channels responding to receptor-dependent activation of phospholipase C. Mammalian (TRPC) channels can form hetero-oligomeric channels in vitro, but native TRPC channel complexes have not been identified to date. We demonstrate here that TRPC1 and TRPC5 are subunits of a heteromeric neuronal channel. Both TRPC proteins have overlapping distributions in the hippocampus. Coexpression of TRPC1 and TRPC5 in HEK293 cells resulted in a novel nonselective cation channel with a voltage dependence similar to NMDA receptor channels, but unlike that of any reported TRPC channel. TRPC1/TRPC5 heteromers were activated by G q-coupled receptors but not by depletion of intracellular Ca 2+ stores. In contrast to the more common view of the TRP family as comprising store-operated channels, we propose that many TRPC heteromers form diverse receptor-regulated nonselective cation channels in the mammalian brain.