Functional significance of altered myosin adenosine triphosphatase activity in enlarged hearts

Abstract

Enlarged hearts secondary to significant pressure overload have a depressed myosin adenosine triphosphatase (ATPase) activity. With mild stress the ATPase activity may be normal or slightly elevated. Enlargement of the heart after exercise or thyroid stress results in an increased ATPase activity. Rapid myothermal techniques, in particular measurements of tension-dependent heat, were used to evaluate: (1) the relation of in vitro measurements of actin-activated ATPase activity to the in vivo behavior of myosin, and (2) the contribution of these changes to the economy of tension development and the time course of crossbridge cycling. Experiments were carried out in animals whose hearts were enlarged secondary to pressure overload (by pulmonary arterial banding) or thyrotoxic stress. In vitro actin-activated ATPase activity levels were 70 and 175 percent of normal for the pressure-overloaded and thyrotoxic hearts, respectively, while the tension-dependent heat per unit tension for the same preparations was, respectively, 78 and 154 percent of normal. Thus there is a reasonable correlation between the in vivo and in vitro measurements of contractile protein ATPase activity, which indicates that the economy of tension development is inversely related to tensiondependent heat per unit tension or actin-activated myosin ATPase activity. Analysis of these data in terms of the kinetics of ATPase activity, crossbridge behavior and tension development leads to the conclusion that in pressure overload hypertrophy the adaptation involves a decrease in the crossbridge cycling rate, an increase in crossbridge off-time and an increase in the on-time of the crossbridge. For thyrotoxic hypertrophy the adaptation involves an increase in the cycling rate, a decrease in the off-time and a decrease in the on-time. The former is adapted for slow, economical tension development and the latter for rapid, less economical tension development.