A common mechanism underlies stretch activation and activation of TRPC6 channels

Maria A. Spassova, Thamara Hewavitharana, Wen Xu, Jonathan Soboloff, Donald L. Gill

Research output: Contribution to journalArticlepeer-review

391 Scopus citations


The TRP family of ion channels transduce an extensive range of chemical and physical signals. TRPC6 is a receptor-activated non-selective cation channel expressed widely in vascular smooth muscle and other cell types. We report here that TRPC6 is also a sensor of mechanically and osmotically induced membrane stretch. Pressure-induced activation of TRPC6 was independent of phospholipase C. The stretch responses were blocked by the tarantula peptide, GsMTx-4, known to specifically inhibit mechanosensitive channels by modifying the external lipid-channel boundary. The GsMTx-4 peptide also blocked the activation of TRPC6 channels by either receptor-induced PLC activation or by direct application of diacylglycerol. The effects of the peptide on both stretch- and diacylglycerol-mediated TRPC6 activation indicate that the mechanical and chemical lipid sensing by the channel has a common molecular mechanism that may involve lateral-lipid tension. The mechanosensing properties of TRPC6 channels highly expressed in smooth muscle cells are likely to play a key role in regulating myogenic tone in vascular tissue.

Original languageEnglish (US)
Pages (from-to)16586-16591
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number44
StatePublished - Oct 31 2006

All Science Journal Classification (ASJC) codes

  • General


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