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Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol

Author

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  • Thomas Hofmann

    (Institut fr Pharmakologie, Universittsklinikum Benjamin Franklin, Freie Universitt Berlin)

  • Alexander G. Obukhov

    (Institut fr Pharmakologie, Universittsklinikum Benjamin Franklin, Freie Universitt Berlin)

  • Michael Schaefer

    (Institut fr Pharmakologie, Universittsklinikum Benjamin Franklin, Freie Universitt Berlin)

  • Christian Harteneck

    (Institut fr Pharmakologie, Universittsklinikum Benjamin Franklin, Freie Universitt Berlin)

  • Thomas Gudermann

    (Institut fr Pharmakologie, Universittsklinikum Benjamin Franklin, Freie Universitt Berlin)

  • Günter Schultz

    (Institut fr Pharmakologie, Universittsklinikum Benjamin Franklin, Freie Universitt Berlin)

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)1. 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 membrane2,3,4; this influx of Ca2+ may5 or may not6 be store-dependent. Drosophila transient receptor potential (TRP) proteins and some mammalian homologues (TRPC proteins) are thought to mediate capacitative Ca2+ entry7,8,9. 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.

Suggested Citation

  • Thomas Hofmann & Alexander G. Obukhov & Michael Schaefer & Christian Harteneck & Thomas Gudermann & Günter Schultz, 1999. "Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol," Nature, Nature, vol. 397(6716), pages 259-263, January.
    • Handle: RePEc:nat:nature:v:397:y:1999:i:6716:d:10.1038_16711
    DOI: 10.1038/16711
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    Cited by:

    1. Amy Clarke & Julia Skerjanz & Mathias A. F. Gsell & Patrick Wiedner & Hazel Erkan-Candag & Klaus Groschner & Thomas Stockner & Oleksandra Tiapko, 2024. "PIP2 modulates TRPC3 activity via TRP helix and S4-S5 linker," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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