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 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.
Morano
I
I
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Hädicke
K
K
Haase
H
H
Böhm
M
M
Erdmann
E
E
Schaub
M C
MC
D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006325:Heart Atria / Q000737:chemistry / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018994:Myosin Light Chains / Q000187:drug effects / Q000378:metabolism*; D010210:Papillary Muscles / Q000378:metabolism; D010766:Phosphorylation; D014335:Tropomyosin / Q000378:metabolism; D019210:Troponin I / Q000378:metabolism
D007527:Isoenzymes; D018994:Myosin Light Chains; D014335:Tropomyosin; D019210:Troponin I; D002118:Calcium