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Increased vascular smooth muscle contractility in TRPC6-/- mice [Erratum in: Mol Cell Biol. vol 25, pg 11191, 2005]

Item Type:Article
Title:Increased vascular smooth muscle contractility in TRPC6-/- mice [Erratum in: Mol Cell Biol. vol 25, pg 11191, 2005]
Creators Name:Dietrich, A. and Mederos y Schnitzler, M. and Gollasch, M. and Gross, V. and Storch, U. and Dubrovska, G. and Obst, M. and Yildirim, E. and Salanova, B. and Kalwa, H. and Essin, K. and Pinkenburg, O. and Luft, F.C. and Gudermann, T. and Birnbaumer, L.
Abstract: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
Keywords:Aorta, Arteries, Barium, Blood Pressure, Calcium Channels, Cations, Complementary DNA, Dependovirus, Electrophysiology, Electroporation, Genetic Models, Genetic Vectors, Ion Channels, Messenger RNA, Muscle Contraction, Muscles, Patch-Clamp Techniques, Phenylephrine, Pressure, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Small Interfering RNA, Smooth Muscle Myocytes, Smooth and Vascular Muscle, TRPC Cation Channels, Time Factors, Western Blotting, Animals, Mice
Source:Molecular and Cellular Biology
Publisher:American Society for Microbiology
Page Range:6980-6989
Date:1 August 2005
Official Publication:https://doi.org/10.1128/MCB.25.16.6980-6989.2005
PubMed:View item in PubMed

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