Effects of amrinone on twitch, tetanus and shortening kinetics in mammalian skeletal muscle.

The contractile effects of amrinone were studied on twitch and tetanus responses of mouse lumbrical muscles. Amrinone (1.1 mM) increased the maximum force level during the tetanus, reduced the rate of rise of force during the onset of tetanus and prolonged the time from the last stimulus to half-relaxation. The rate of redevelopment of force after a release during the tetanus plateau was likewise reduced. Amrinone (greater than or equal to 0.5 mM) increased the time to peak twitch force and the time to half-relaxation during the twitch. The peak twitch force was not significantly changed. The force-velocity relation was markedly affected by amrinone: there was a decrease in maximum velocity of shortening, an increase in maximum isometric force and a decrease in curvature of the force-velocity relation. The results suggest that amrinone modulates the kinetic properties of the myosin cross-bridges by exerting a specific effect upon the myofilament system. The latter effects are mainly responsible for the contractile changes produced by amrinone in mouse skeletal muscle. Amrinone appears to have little effect on the metabolism of activator calcium in this particular preparation.