title: A common mechanism underlies stretch activation and receptor activation of TRPC6 channels.
abstract: The TRP family of ion channels transduce an extensive range of chemical and physical signals. TRPC6 is a receptor-activated nonselective 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD 21201, USA. mspas001@umaryland.edu
authors.forename: Maria A
authors.initials: MA
authors.lastname: Spassova
authors.forename: Thamara
authors.initials: T
authors.lastname: Hewavitharana
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Soboloff
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gill
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004594:Electrophysiology; D006801:Humans; D009997:Osmotic Pressure; D018408:Patch-Clamp Techniques; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D050052:TRPC Cation Channels