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Home  > Press Release  > Overexpression of heart-specific small subunit of myosin light chain phosphatase results in heart failure and conduction disturbance.

Overexpression of heart-specific small subunit of myosin light chain phosphatase results in heart failure and conduction disturbance.

Abstract

Mutations in genes encoding components of sarcomere cause cardiomyopathy, which is often associated with abnormal Ca2+ sensitivity of muscle contraction. We previously showed that a heart-specific myosin light chain phosphatase small subunit, hHS-M21, increases the Ca2+-sensitivity of muscle contraction. The aim of this study was to investigate the function of hHS-M21 in vivo and the causative role of abnormal Ca2+ sensitivity in cardiomyopathy. We generated transgenic (Tg) mice with cardiac-specific overexpression of hHS-M21. We confirmed that hHS-M21 increased the Ca2+ sensitivity of cardiac muscle contraction in vivo, which was not followed by an increased phosphorylation of myosin light chain 2 (MLC2) isoforms. The hHS-M21 Tg mice developed severe systolic dysfunction with myocardial fibrosis and degeneration of cardiomyocytes in association with sinus bradycardia and atrioventricular conduction defect. The contractile dysfunction and cardiac fibrosis were improved by treatment with Rho-kinase inhibitor Fasudil. Our findings implied that the overexpression of hHS-M21 results in cardiac dysfunction and conduction disturbance via non-MLC2-phosphorylation-dependent regulation.

Journal Article

JOUNAL:
American Journal of Physiology, Heart and Circulation Physiology

TITLE:
Overexpression of heart-specific small subunit of myosin light chain phosphatase results in heart failure and conduction disturbance.

DOI:
https://doi.org/10.1152/ajpheart.00696.2017

Correspondence to

Akinori KIMURA, Professor
Department of Molecular Pathogenesis
Medical Research Institute
Tokyo Medical and Dental University(TMDU)
E-mail: akitis(at)mri.tmd.ac.jp