Effects of tilisolol, a nonselective beta-adrenergic blocker, on the membrane currents of isolated guinea pig ventricular myocytes

The effects of tilisolol, a nonselective beta-adrenoceptor blocker, on transmembrane ionic currents were studied in single guinea pig ventricular myocytes by using the whole-cell voltage clamp technique. In the absence of beta-adrenergic stimulation, 10 mu M tilisolol, a concentration higher than that used in the clinical therapeutic regimen, did not affect the L-type Ca2+ current (I-Ca), the inwardly rectifying K+ current (I-Kl), or the delayed rectifying K+ current (I-K). In addition, it did not induce currents through the adenosine triphosphate (ATP)-sensitive K+ channels. However, under the nonselective P-adrenergic stimulation with 1 mu M isoproterenol, 1 mu M tilisolol almost completely reversed the agonist-induced increase of I-K. The increase of I-Ca by isoproterenol was blocked only by similar to 30% with tilisolol. We concluded that, at therapeutic concentrations (0.01-0.15 mu M), tilisolol is a pure beta-adrenoceptor antagonist that has no direct effects on the transmembrane ionic currents of mammalian ventricular myocytes, such as I-Ca, I-Kl, or I-K. Comparison of the dose-dependent effects of tilisolol on I-Ca and I-K suggested that tilisolol may selectively inhibit catecholamine-induced increase of I-K at the therapeutic concentrations. The virtually selective inhibition of I-K, leaving I-Ca intact, may be favorable to prevent the catecholamine-induced arrhythmia without inhibiting contraction.