Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol

Thomas Hofmann, Alexander G. Obukhov, Michael Schaefer, Christian Harteneck, Thomas Gudermann, Günter Schultz

Research output: Contribution to journalArticle

1158 Scopus citations

Abstract

Eukaryotic cells respond to many hormones and neurotransmitters with increased activity of the enzyme phospholipase C and a subsequent rise in the concentration of intracellular free calcium ([Ca2+](i)). The increase in [Ca2+](i) occurs as a result of the release of Ca2+ from intracellular stores and an influx of Ca2+ through the plasma membrane; this influx of Ca2+ may or may not be store-dependent. Drosophila transient receptor potential (TRP) proteins and some mammalian homologues (TRPC proteins) are thought to mediate capacitative Ca2+ entry. Here we describe the molecular mechanism of store-depletion-independent activation of a subfamily of mammalian TRPC channels. We find that hTRPC6 is a non-selective cation channel that is activated by diacylglycerol in a membrane-delimited fashion, independently of protein kinases C activated by diacylglycerol. Although hTRPC3, the closest structural relative of hTRPC6, is activated in the same way, TRPCs 1, 4 and 5 and the vanilloid receptor subtype 1 are unresponsive to the lipid mediator. Thus, hTRPC3 and hTRPC6 represent the first members of a new functional family of second-messenger-operated cation channels, which are activated by diacylglycerol.

Original languageEnglish (US)
Pages (from-to)259-263
Number of pages5
JournalNature
Volume397
Issue number6716
DOIs
StatePublished - Jan 21 1999

ASJC Scopus subject areas

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    Hofmann, T., Obukhov, A. G., Schaefer, M., Harteneck, C., Gudermann, T., & Schultz, G. (1999). Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature, 397(6716), 259-263. https://doi.org/10.1038/16711