Increased vascular smooth muscle contractility in TRPC6-/- mice.

Published

Journal Article

Among the TRPC subfamily of TRP (classical transient receptor potential) channels, TRPC3, -6, and -7 are gated by signal transduction pathways that activate C-type phospholipases as well as by direct exposure to diacylglycerols. Since TRPC6 is highly expressed in pulmonary and vascular smooth muscle cells, it represents a likely molecular candidate for receptor-operated cation entry. To define the physiological role of TRPC6, we have developed a TRPC6-deficient mouse model. These mice showed an elevated blood pressure and enhanced agonist-induced contractility of isolated aortic rings as well as cerebral arteries. Smooth muscle cells of TRPC6-deficient mice have higher basal cation entry, increased TRPC-carried cation currents, and more depolarized membrane potentials. This higher basal cation entry, however, was completely abolished by the expression of a TRPC3-specific small interference RNA in primary TRPC6(-)(/)(-) smooth muscle cells. Along these lines, the expression of TRPC3 in wild-type cells resulted in increased basal activity, while TRPC6 expression in TRPC6(-/-) smooth muscle cells reduced basal cation influx. These findings imply that constitutively active TRPC3-type channels, which are up-regulated in TRPC6-deficient smooth muscle cells, are not able to functionally replace TRPC6. Thus, TRPC6 has distinct nonredundant roles in the control of vascular smooth muscle tone.

Full Text

Duke Authors

Cited Authors

  • Dietrich, A; Mederos Y Schnitzler, M; Gollasch, M; Gross, V; Storch, U; Dubrovska, G; Obst, M; Yildirim, E; Salanova, B; Kalwa, H; Essin, K; Pinkenburg, O; Luft, FC; Gudermann, T; Birnbaumer, L

Published Date

  • August 2005

Published In

Volume / Issue

  • 25 / 16

Start / End Page

  • 6980 - 6989

PubMed ID

  • 16055711

Pubmed Central ID

  • 16055711

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/MCB.25.16.6980-6989.2005

Language

  • eng

Conference Location

  • United States