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

Department of Anesthesiology and Critical Care Medieine, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan

Seiko Kawano

Department of Cardiovascular Diseases, Medical Research Institute

Masayasu Hiraoka

Department of Cardiovascular Diseases, Medical Research Institute

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 (I_K), while the drug little affected the inward rectified K+ current (I_KI). Applications of 10 µM and 100 µM tilisolol reduced the maximal conductance of I_K 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 I_Ca.L, in addition to its beta-receptor blocking action.

Key Words: tilisolol • delayed rectified K+ current (IK) • L-type2+ current (ICa.L) • guinea pig ven tricular myocytes.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 1, No. 1, 41-48 (1996)
DOI: 10.1177/107424849600100107


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