埼玉医科大学雑誌 第31巻 第2号 (2004年4月) 103-113頁 ◇論文(図表を含む全文)は,PDFファイルとなっています.
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原 著
心筋細胞興奮収縮連関におよぼす第3のキナーゼ系Rhoキナーゼの役割について
茆原 るり
埼玉医科大学第二内科学教室〔平成16年1月13日 受付〕
The Role of Rho Kinase : Third Kinase System in the Regulation of Excitation-Contraction
Coupling of Cardiac Muscle
Ruri Chihara (Second Department of Internal Medicine, Moroyama, Iruma-gun,
Saitama 350-0495, Japan)
It has been known that various neurohumoral factors play important roles
in the regulation of contraction and relaxation in cardiac muscle. Earlier
reports suggested that angiotensin II play important roles in the pathogensis
of chronic heart failure. However, the roles of endothelin 1 have not
been fully clarified. Thus, we investigated the roles of endothelin in
excitation-contraction coupling and relaxation in isolated single ventricular
myocytes. We focused on the third kinase system: Rho dependent protein
kinase (ROCK) in addition to the protein kinase A and C. We isolated
single ventricular myocytes from Wister rats and measured intracellular
calcium transients and cell contraction simultaneously. When we pretreated
cells with PKC inhibitor, exposure to endothelin-1 still produced positive
inotropic and lusitrophic effects. These effects were not observed
when cells were pretreated with PKC inhibitor and ROCK inhibitor or myosin
light chain kinase inihibitor. Effects of myosin light chain phosphatase
inhibitor simulated those of endothelin-1. Inhibition of myosin light
chain phosphatase accelerated the phosphorylation status of cardiac myosin
light chain resulting in positive inotropic action similar to endothelin-1.
Our results suggested that endothelin might activate myosin light chain
not only via PKC but also via ROCK pathway.
Our working hypothesis is that endothelin 1 may produce positive inotropic
effects via ROCK pathway. Thus we try to reveal the role of ROCK pathway
in the regulation of contraction and relaxation in cardiac muscle.
Keywords: Endothelin, Cardiac muscle, Myosin light chain, Rho kinase,
Protein kinase C, Excitation-contraction coupling
J Saitama Med School 2004;31:103-113
(Received January 13, 2004)
(C) 2004 The Medical Society of
Saitama Medical School
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