Effects of amrinone on the contractile behaviour of frog striated muscle fibres.

The effects of amrinone (0.005-2.1 mM) were studied on isolated single muscle fibres of the frog (0.6-4.3 degrees C). In the concentrations used amrinone potentiated the isometric twitch, increased the initial rate of force development and prolonged the time to peak twitch force and the time from peak force to half relaxation. There was a moderate but statistically significant (P less than 0.001) enhancement of the maximum tetanic force and a marked slowing of the relaxation phase of the tetanus. Amrinone depressed the velocity of unloaded shortening by 33 +/- 2% (mean +/- SE, n = 6) and reduced the curvature of the force-velocity relation leading to an increase of a/Po in Hill's (1938) hyperbolic equation. In accordance with the effects of amrinone on the force-velocity relation, there was a decrease in the rate of redevelopment of force after the fibre was released to zero tension during the tetanus plateau. The evidence suggests that the drug affects the contractile properties of frog muscle fibres by two different mechanisms: (I) amrinone affects the excitation-contraction coupling causing enhanced calcium release in response to membrane excitation and (2) amrinone exerts a direct effect on the kinetics of turnover of the myosin cross-bridges. The latter aspect of the drug effect was evaluated in terms of A.F. Huxley's (1957) cross-bridge model by means of a computer program.