TRPC1 and TRPC5 form a novel cation channel in mammalian brain.
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.
Strübing
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C
Howard Hughes Medical Institute, Cardiovascular Research, Children's Hospital, 320 Longwood Avenue, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Krapivinsky
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Krapivinsky
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Clapham
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DE
D000818:Animals; D001369:Axons / Q000737:chemistry; D001923:Brain Chemistry; D002118:Calcium / Q000032:analysis; D015220:Calcium Channels / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D027682:Cation Transport Proteins; D002412:Cations; D002460:Cell Line; D003712:Dendrites / Q000737:chemistry; D004553:Electric Conductivity; D004622:Embryo, Mammalian; D015870:Gene Expression; D006624:Hippocampus / Q000737:chemistry; D006801:Humans; D007473:Ion Channels / Q000737:chemistry*; D007668:Kidney; D046911:Macromolecular Substances; D009474:Neurons / Q000737:chemistry / Q000648:ultrastructure; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D050052:TRPC Cation Channels; D014162:Transfection
D015220:Calcium Channels; D027682:Cation Transport Proteins; D002412:Cations; D007473:Ion Channels; D046911:Macromolecular Substances; D016194:Receptors, N-Methyl-D-Aspartate; D050052:TRPC Cation Channels; C491780:TRPC5 protein, human; C503500:Trpc5 protein, rat; C096351:transient receptor potential cation channel, subfamily C, member 1; D002118:Calcium