Changes in essential myosin light chain isoform expression provide a molecular basis for isometric force regulation in the failing human heart

J Mol Cell Cardiol. 1997 Apr;29(4):1177-87. doi: 10.1006/jmcc.1996.0353.


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 pCa50 of 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Calcium / pharmacology
  • Female
  • Heart Atria / chemistry
  • Heart Atria / metabolism
  • Heart Failure / metabolism*
  • Humans
  • Isoenzymes
  • Isometric Contraction / drug effects
  • Isometric Contraction / physiology*
  • Male
  • Middle Aged
  • Muscle Fibers, Skeletal / metabolism
  • Myosin Light Chains / drug effects
  • Myosin Light Chains / metabolism*
  • Papillary Muscles / metabolism
  • Phosphorylation
  • Tropomyosin / metabolism
  • Troponin I / metabolism


  • Isoenzymes
  • Myosin Light Chains
  • Tropomyosin
  • Troponin I
  • Calcium