A Model for Regulation of the Mg2+-Stimulated Acto-Myosin-ATPase Activity: Inhibition of the Formation of Actin-Myosin Complex and the Mg2+-Stimulated Acto-Myosin-ATPase Activity by IMP and AMP

Abstract

Previously, we showed that the decrease in force output during continuous isometric contractions in rat skeletal muscle was related to an increase in the concentration of IMP. In this paper we report on additional experiments in which the effect of IMP on the Mg 2+ -stimulated acto-myosin-ATPase activity of isolated actin and myosin is measured at 35°C. The results show that 1) the binding of actin to myosin is co-operative (Hill coefficient = 3.82); 2) in the presence of IMP or AMP the Mg 2+ -stimulated acto-myosin-ATPase activity is inhibited up to 60% at 10 mM; 3) in the presence of IMP or AMP not only the Mg 2+ -stimulated acto-myosin-ATPase activity decreases, but also K 50. From these results we conclude that IMP and AMP may be considered as uncompetitive inhibitors. Our results suggest that IMP and AMP can prevent an ‘energy crisis’ during exhaustive exercise of short duration by down-regulating the contractile machinery.