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 journalArticle

285 Citations (Scopus)

Abstract

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
Volume103
Issue number44
DOIs
StatePublished - Oct 31 2006

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Diglycerides
Lipids
Peptides
Smooth Muscle Myocytes
Type C Phospholipases
Ion Channels
Vascular Smooth Muscle
Blood Vessels
Cations
Pressure
Membranes
Grammostola spatulata MTx4 protein

All Science Journal Classification (ASJC) codes

  • General

Cite this

Spassova, Maria A. ; Hewavitharana, Thamara ; Xu, Wen ; Soboloff, Jonathan ; Gill, Donald L. / A common mechanism underlies stretch activation and activation of TRPC6 channels. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 44. pp. 16586-16591.
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A common mechanism underlies stretch activation and activation of TRPC6 channels. / Spassova, Maria A.; Hewavitharana, Thamara; Xu, Wen; Soboloff, Jonathan; Gill, Donald L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 44, 31.10.2006, p. 16586-16591.

Research output: Contribution to journalArticle

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