EFFECT OF CATECHOLAMINE ANALOGS ON CONTROL OF ACTOMYOSIN BY NATIVE TROPOMYOSIN AND CALCIUM; THE NATURE OF THE NEGATIVE INOTROPIC RECEPTOR

¹ Department of Physiology, University of Rochester, Rochester, New York

Catecholamine analogs increase the amount of Ca required to activate the adenosine triphosphatase (ATPase) of cardiac myosin B but do not change the maximum rate of adenosine triphosphate hydrolysis attained at high Ca concentrations. Data indicate that catecholamine analogs are competitive inhibitors which decrease the affinity of myosin B for Ca. At the pCa at which inhibition is maximal, 5 x 10^-4 M dichloroisoproterenol or propranolol halve ATPase activity. Similar results were obtained with skeletal myosin B, but threshold was 50-fold higher and extent of inhibition was smaller. If native tropomyosin is removed from cardiac myosin B, responsiveness to Ca and catecholamine analogs is lost. Replacement of freshly isolated native tropomyosin restores responsiveness to both agents. Aged native tropomyosin restores Ca control but not responsiveness to drugs, indicating that the negative inotropic receptor is not the Ca binding site per se. Of the various components of native tropomyosin, the Ca-binding moiety is essential but not sufficient. We conclude that the functional receptor is the entire native tropomyosin complex. Discussion considers the interaction of intracellular receptors in determining the magnitude and time course of tension in vivo.