Regulation of arterial tone by smooth muscle myosin type II

Item Type:	Article
Title:	Regulation of arterial tone by smooth muscle myosin type II
Creators Name:	Loehn, M. and Kaempf, D. and Chai, G.X. and Haller, H. and Luft, F.C. and Gollasch, M.
Abstract:	The initiation of contractile force in arterial smooth muscle (SM) is believed to be regulated by the intracellular Ca2+concentration and SM myosin type II phosphorylation. We tested the hypothesis that SM myosin type II operates as a molecular motor protein in electromechanical, but not in protein kinase C (PKC)-induced, contraction of small resistance-sized cerebral arteries. We utilized a SM type II myosin heavy chain (MHC) knockout mouse model and measured arterial wall Ca2+ concentration ([Ca2+]i) and the diameter of pressurized cerebral arteries (30–100 {mu}m) by means of digital fluorescence video imaging. Intravasal pressure elevation caused a graded [Ca2+]i increase and constricted cerebral arteries of neonatal wild-type mice by 20–30%. In contrast, intravasal pressure elevation caused a graded increase of [Ca2+]i without constriction in (−/−) MHC-deficient arteries. KCl (60 mM) induced a further [Ca2+]i increase but failed to induce vasoconstriction of (−/−) MHC-deficient cerebral arteries. Activation of PKC by phorbol ester (phorbol 12-myristate 13-acetate, 100 nM) induced a strong, sustained constriction of (−/−) MHC-deficient cerebral arteries without changing [Ca2+]i. These results demonstrate a major role for SM type II myosin in the development of myogenic tone and Ca2+-dependent constriction of resistance-sized cerebral arteries. In contrast, the sustained contractile response did not depend on myosin and intracellular Ca2+ but instead depended on PKC. We suggest that SM myosin type II operates as a molecular motor protein in the development of myogenic tone but not in pharmacomechanical coupling by PKC in cerebral arteries. Thus PKC-dependent phosphorylation of cytoskeletal proteins may be responsible for sustained contraction in vascular SM.
Keywords:	Protein Kinase C, Pressurized Cerebral Arteries, Phorbol Ester, Arterial Tone, Myosin Heavy Chain, Knockout Mouse, Animals, Mice
Source:	American Journal of Physiology Cell Physiology
ISSN:	0363-6143
Volume:	283
Number:	5
Page Range:	C1383-C1389
Date:	1 November 2002
Official Publication:	https://doi.org/10.1152/ajpcell.01369.2000
PubMed:	View item in PubMed

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