Electrophysiologic Effects of Beta-blocking Agent, Tilisolol; on Isolated Guinea Pig Ventricular Myocytes

Abstract

Background: Electrophysiologic effects of a beta-blocking agent, tilisolol, were studied with isolated guinea pig ventricular myocytes using the whole cell patch clamp technique. Methods and Results:. Tilisolol at 10 μM or higher concentrations prolonged action poten tial duration (APD) at 90% repolarization (APD90) and at 100 μM or higher concentrations shortened APD at 20% repolarization (APD20) without changes in resting membrane poten tial. At 10 μM concentration tilisolol prolonged APD90 from 236.6 ± 55.3 ms in the control to 253.4 ± 52.4 ms (n = 16; P < .0 L), while APD20 was unaffected. At 100 μM tilisolol, APD20 was shortened from 143.6 ± 15.7 ms in the control to 133.7 ± 22.6 ms (n = 8; P < .05). Under voltage clamp, tilisolol decreased the delayed rectifier K+ current (IK), while the drug little affected the inward rectified K+ current (IKI). Applications of 10 μM and 100 μM tilisolol reduced the maximal conductance of IK by 35.7 ± 3.5% and 47.4 ± 3.5% of the control, respectively, without changes in voltage dependence (n = 10). Tilisolol at 100 μM decreased the L-type Ca2+, current (I Ca.L) by 22.0 ± 9.8% (n = 6) of the control, and the inactivation curve was shifted to a hyperpolarizing direction. Conclusions: Tilisolol has a direct membrane action to depress IK and ICa.L, in addition to its beta-receptor blocking action.