Biphasic effects of acetylstrophanthidin on automaticity in guinea pig ventricular muscle

The effects of acetylstrophanthidin (AS) on depolarization-induced automaticity and contractility of guinea pig papillary muscle were studied in a single sucrose gap chamber with microelectrode and current-clamp techniques. The concentration used, 1.4-1.8 microM, never induced automaticity in preparations at their normal resting potential. Twenty min after superfusion with AS, action potential duration (APD) was prolonged and the force of contraction increased. These were associated with an increase in slope of phase 4 depolarization and an increase in the membrane resistance (Rm) of muscles depolarized with small constant current pulses. With longer (50-80 min) periods of AS superfusion, APD became shorter, Rm decreased to less than predrug values, and in depolarized preparations, the slope of phase 4 decreased. Contractility remained unchanged throughout this second phase. All of these effects were fully reversible upon 60 min of superfusion with AS-free Tyrode solution. We suggest that the biphasic effects of AS on the automaticity of depolarized ventricular muscle cells are caused by an initial decrease followed by a later increase in transmembrane potassium conductance.