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 (M LC) isoforms on the Ca2+ sensitivity of isometric force production of demembranated (skinned) fibers of papillary muscle from the left ventr icle of three groups: patients with ischemic cardiomyopathy, patients with dilated cardiomyopathy (NYHA IV) and normal human hearts. Express ion and phosphorylation of the phosphorylatable MLC isoforms (MLC-2) w as equal within all three groups. However, 72% of the patients investi gated in this study expressed the atrial essential MLC, (ALC-1) in add ition to the essential ventricular MLC (VLC-1) ranging between 2.4% an d 10.3%. Using fibers from failing hearts, we observed a significant p ositive correlation between ALC-1 and Ca2+ sensitivity in that the hig her the ALC-1 expression the higher the Ca2+ sensitivity: pCa(50) (Ca2 + required for half-maximal force production) was 5.87 without ALC-1 a nd 6.08 with 10.3% ALC-1. Fibers from a normal heart (no ALC-1) reveal ed a pCa(50) of 5.85. Isoform and phosphorylation patterns of tropomyo sin and troponin I remained unchanged in the patients and normal heart s. Our results suggest that Ca2+ responsiveness and force development of the human heart is regulated by the expression of different MLC-1 i soforms. (C) 1997 Academic Press Limited.