SC-35135 was evaluated in guinea pig papillary muscle using standard microelectrode techniques to record transmembrane action potentials. SC-35135 markedly blocked Vmax (maximum rate of membrane depolarization) as a function of pacing frequency in the concentration range of 3 x 10(-6) to 3 x 10(-5) M, and was without effect on action potential duration. The effective refractory period was significantly shortened only at the highest concentration tested (3 x 10(-5) M). Rate constants for the onset of Vmax block determined at two stimulation rates, 60 and 200 pulses/min, were 0.17 +/- 0.052 and 0.06 +/- 0.005 (action potentials)-1, respectively, in the presence of 10(-5) M SC-35135. The recovery from Vmax depression following a train of stimuli was very slow in the presence of SC-35135. The average time constant for the recovery from block of Vmax after addition of 10(-5) M SC-35135 was 10.2 +/- 0.94 s. SC-35135 caused both a concentration- and stimulation frequency-dependent hyperpolarizing shift in the half point of the relationship between Vmax and resting membrane potential. Slow response (Ca current-dependent) action potentials were not changed by SC-35135 at concentrations less than or equal to 3 x 10(-5) M, indicating a lack of class IV antiarrhythmic activity.