Changes in Essential Myosin Light Chain Isoform Expression Provide a Molecular Basis for Isometric Force Regulation in the Failing Human Heart

We investigated the effects of the expression of myosin light chain (MLC) isoforms on the Ca2+sensitivity of isometric force production of demembranated (skinned) fibers of papillary muscle from the left ventricle of three groups: patients with ischemic cardiomyopathy, patients with dilated cardiomy...

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Bibliographic Details
Published in:Journal of molecular and cellular cardiology 1997-04, Vol.29 (4), p.1177-1187
Main Authors: Morano, Ingo, Hädicke, Kerstin, Haase, Hannelore, Böhm, Michael, Erdmann, Erland, Schaub, Marcus C.
Format: Article
Language:English
Subjects:
Calcium - metabolism
Calcium - pharmacology
Calcium sensitivity
Cardiomyopathy
Female
Heart Atria - chemistry
Heart Atria - metabolism
Heart Failure - metabolism
Human failing heart
Humans
Isoenzymes
Isometric Contraction - drug effects
Isometric Contraction - physiology
Male
Middle Aged
Muscle Fibers, Skeletal - metabolism
Myosin light chains
Myosin Light Chains - drug effects
Myosin Light Chains - metabolism
Papillary Muscles - metabolism
Phosphorylation
Tropomyosin - metabolism
Troponin I - metabolism
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Summary:We investigated the effects of the expression of myosin light chain (MLC) isoforms on the Ca2+sensitivity of isometric force production of demembranated (skinned) fibers of papillary muscle from the left ventricle of three groups: patients with ischemic cardiomyopathy, patients with dilated cardiomyopathy (NYHA IV) and normal human hearts. Expression and phosphorylation of the phosphorylatable MLC isoforms (MLC-2) was equal within all three groups. However, 72% of the patients investigated in this study expressed the atrial essential MLC (ALC-1) in addition to the essential ventricular MLC (VLC-1) ranging between 2.4% and 10.3%. Using fibers from failing hearts, we observed a significant positive correlation between ALC-1 and Ca2+sensitivity in that the higher the ALC-1 expression the higher the Ca2+-sensitivity: pCa50(Ca2+required for half-maximal force production) was 5.87 without ALC-1 and 6.08 with 10.3% ALC-1. Fibers from a normal heart (no ALC-1) revealed a pCa50of 5.85. Isoform and phosphorylation patterns of tropomyosin and troponin I remained unchanged in the patients and normal hearts. Our results suggest that Ca2+responsiveness and force development of the human heart is regulated by the expression of different MLC-1 isoforms.
ISSN:0022-2828
1095-8584
DOI:10.1006/jmcc.1996.0353