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

1997; Elsevier BV; Volume: 29; Issue: 4 Linguagem: Inglês

10.1006/jmcc.1996.0353

1095-8584

Ingo Morano, Kerstin Hädicke, Hannelore Haase, Michael Böhm, Erland Erdmann, Marcus Schaub,

Cardiovascular Effects of Exercise

Abstract We investigated the effects of the expression of myosin light chain (MLC) isoforms on the Ca 2+ 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 Ca 2+ sensitivity in that the higher the ALC-1 expression the higher the Ca 2+ -sensitivity: pCa 50 (Ca 2+ 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 pCa 50 of 5.85. Isoform and phosphorylation patterns of tropomyosin and troponin I remained unchanged in the patients and normal hearts. Our results suggest that Ca 2+ responsiveness and force development of the human heart is regulated by the expression of different MLC-1 isoforms.