DRUG EFFECTS ON CARDIAC MYOSIN ADENOSINE TRIPHOSPHATASE ACTIVITY

¹ Department of Medicie, Robinette Foundation, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania

Various agents known to alter cardiac contractility were examined for their effect on dog cardiac myosin adenosine triphosphatase (ATPase) activity. Anesthetic agents were shown to have either the same, or no effect, on cardiac myosin ATPase activity which persisted through the extraction and purification phase. No stimulatory or depressant effect on enzyme activity was observed when quinidine, procaine amide, angiotensin, digitoxin, digoxin, ouabain or inotropic sympathomimetic amines were incubated with normal cardiac myosin. Myosin obtained from dogs with "spontaneously" occurring congestive heart failure also exhibited no change in enzyme activity in the presence of digoxin or the inotropic sympathomimetic amines. Calcium and magnesium ions, however, had an effect on cardiac myosin ATPase activity which correlated with their in vivo action on cardiac contractility. The effect of magnesium and calcium on myosin enzyme activity was studied further. The association constant between calcium and myosin is 1.8 x 10⁴ with eight binding sites on the myosin molecule for calcium. Calcium activation of myosin ATPase activity appears to relate to the formation of calcium-ATP rather than to a direct effect of calcium on the myosin enzyme site. The inhibitory effect of magnesium on calcium-activated myosin ATPase activity could not be related to reduced calcium-ATP formation or to a direct effect of magnesium on the myosin molecule.