Regulatory proteins in hamster cardiomyopathy.
We have shown in genetic myopathic hamsters that cardiac myofibrillar ATPase regulation by calcium is altered and that there are shifts in myosin isozyme distribution (V1----V3) suggesting abnormalities in multiple components of the contractile apparatus. To focus more on the regulatory proteins (troponin and tropomyosin), individual proteins of the skeletal and cardiac actomyosin system were reconstituted under controlled conditions. In this way, myosin plus actin and troponin-tropomyosin from the normal and myopathic animals could be studied enzymatically. The proteins were isolated from the skeletal or cardiac muscle of random-bred control and cardiomyopathic hamsters (BIO 53:58) at 7 months of age. Sodium dodecyl sulfate gel electrophoretic patterns indicated differences in the troponin I and troponin C regions of myopathic skeletal muscle, but cardiac samples from control and myopathic hamsters showed similarities in their mobilities. This suggests the possibility of different cardiac isozymes in the regulatory protein complex, as reported in our previous studies of cardiac myosin in cardiomyopathy. Calcium sensitivity was markedly decreased in the actomyosin reconstituted with troponin-tropomyosin from skeletal as well as cardiac muscle from myopathic animals. In summary, our data show that the regulatory proteins in skeletal and cardiac muscle of the myopathic hamsters have decreased inhibitory action on Mg2(+)-actomyosin ATPase activity. This loss of calcium regulation along with shifts in cardiac myosin heavy chain may be partially responsible for the impaired cardiac function in the hearts of myopathic hamsters.
Malhotra
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Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York.
D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009202:Cardiomyopathies / Q000235:genetics / Q000503:physiopathology*; D006224:Cricetinae; D003720:Densitometry; D004533:Egtazic Acid / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D008297:Male; D008647:Mesocricetus / Q000235:genetics; D009132:Muscles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D051381:Rats; D014335:Tropomyosin / Q000502:physiology*; D014336:Troponin / Q000502:physiology*
D014335:Tropomyosin; D014336:Troponin; D004533:Egtazic Acid; D017301:Ca(2+) Mg(2+)-ATPase; D009218:Myosins; D000252:Calcium-Transporting ATPases; D002118:Calcium