MYOCARDIAL-INFARCTION AND REGULATORY MYOSIN LIGHT-CHAIN

Myosin from cardiac muscle consists of two heavy chains and two pairs of light chain. Regulatory myosin light chain (RMLC) is phosphorylated by a Ca2+ and calmodulin dependent myosin light chain kinase. The imp act of experimental myocardial infarction on cardiac RMLC was studied. The left anterior descending coronary artery of rabbits was ligated. Three, 7 and 14 days later the animals were euthanized, sections of th e heart were frozen in liquid nitrogen and later subjected to 2-dimens ional electrophoresis. Isoelectric focusing was carried out at a pH ra nge of 4.5-5.4. Reproducible patterns of protein separation showed fou r spots with proteins of phosphorylatable regulatory light chains shif ted to a more negative pH as compared to essential light chain. We inv estigated changes in phosphorylation of RMLC in infarcted heart muscle . As compared to sham operated animals, a decline in phosphorylation o f RMLC was present in both infarcted and non-infarcted portions of the left ventricle; the latter was significant 7 days following the onset of ischemia. In contrast, the decline in percent phosphorylation in t he infarcted area was not significant. The amount of RMLC decreased si gnificantly in the infarcted portion. A highly significant reduction i n the percent of viable cardiomyocytes accompanied the decline in phos phorylation. There was a significant correlation of RMLC following adm inistration of isoproterenol, 7 and 14 days following onset of ischemi a. Only faint traces of essential atrial myosin light chain (ALC-1) we re present in the non-infarcted portion of the left ventricle. No corr elation was found between percent phosphorylation and the amount of RM LC (density) following infusion of saline or isoproterenol. Isoprotere nol significantly increased percent phosphorylation without altering t he amount of RMLC protein. We conclude that myocardial infarction prof oundly affects regulatory myosin light chain phosphorylation in the in farcted and non-infarcted areas of the myocardium and that RMLC plays a significant part in myocardial contracility. (C) 1997 Academic Press Limited.