Troponin-tropomyosin abnormalities in hamster cardiomyopathy.
Cardiac myofibrils from cardiomyopathic hamsters exhibit elevated Mg2+ ATPase activity and a parallel upward shift of the calcium ATPase dose response curve. To explore the mechanism, myofibrils from control and cardiomyopathic hamster hearts were incubated with isolated troponin-tropomyosin complex (Tn.Tm) from cardiomyopathic and control hamster or from dog hearts. Tn.Tm from control hamster or dog hearts restored normal Mg2+ ATPase activities to myofibrils from myopathic hearts. However, the maximum ATPase response to calcium stimulation was less in cardiomyopathic myofibrils compared to controls, even when control Tn.Tm was included. Electrophoretic patterns of Tn.Tm from myopathic and control hearts were similar. Electrophoresis of the hamster myofibrils mixed with dog cardiac Tn.Tm and then washed demonstrated binding of this complex to myopathic myofibrils. To further confirm that the incubation experiments resulted in binding, 125I troponin-tropomyosin was cross-hybridized with myofibrils, extensively washed, and then analyzed enzymatically and autoradiographically. Autoradiograms demonstrated similar percent binding of 125I Tn.Tm to all myofibrillar preparations and enzymatic effects like those found using cold Tn.Tm. These studies suggest that Tn.Tm from cardiomyopathic hearts inhibits Mg2+ myofibrillar ATPase activity to a lesser degree than Tn.Tm from control hearts. Decreased stimulation by calcium in myopathic preparations may be due to abnormalities in troponin-tropomyosin and/or to the decreased myosin ATPase activity observed previously.
Malhotra
A
A
Department of Medicine, Montefiore Medical Center, Bronx, New York 10467.
Scheuer
J
J
D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D009202:Cardiomyopathies / Q000503:physiopathology*; D006224:Cricetinae; D004285:Dogs; D046911:Macromolecular Substances; D009206:Myocardium / Q000201:enzymology*; D009218:Myosins / Q000378:metabolism*; D014335:Tropomyosin / Q000502:physiology*; D014336:Troponin / Q000502:physiology*
D046911:Macromolecular Substances; D014335:Tropomyosin; D014336:Troponin; D017301:Ca(2+) Mg(2+)-ATPase; D009218:Myosins; D000252:Calcium-Transporting ATPases; D002118:Calcium