Differential effects ofd, l-Sotalol andd-Sotalol on isoproterenol-increased delayed rectifier outward potassium current in guinea pig single ventricular myocytes

Abstract

The aim of this study was to compare the effects ofd, l-Sotalol andd-Sotalol on the delayed rectifier K⁺ outward current in the presence of isoproterenol at different concentrations. Time-dependent delayed rectifier K⁺ outward currents were measured in isolated guinea pig single myocytes using the whole-cell configuration of the patch-clamp technique. Currents were measured in response to 300 ms depolarizing pulses from a holding potential of −40 mV in three experimental protocols [control, isoproterenol (10^-9mollL-10^-6 mollL), and isoproterenol (10^-9mollL-10^-6mollL) plus eitherd, l-Sotalol (10^-4 mollL) ord-Sotalol (10^-4 mollL)]. I_k tail currents were measured upon repolarization to −40 mV. It was found that Ik was significantly amplified in the presence of isoproterenol (10^-9 mollL-10^-6 mollL) plusd-Sotalol. At 10^-8 mollL isoproterenol, I_k was increased by 92. 7%± 17. 1% (P<0. 05) and 54. 3 %±13. 4% afterd-Sotalol addition (P<0. 05). In contrast,d, l-Sotalol completely conteracted the increase of I_k by isoproterenol (<10^-8 mollL), and compared to control, Ik was decreased by 35. 6%± 8. 1 % at 10^-8 mollL isoproterenol plusd, l-Sotalol (P<0. 05). It is concluded that the β-adrenergic blocking property ofd, l-Sotalol but not that ofd-Sotalol maintains the delayed rectifier K⁺ outward current blockade in the presence of isoproterenol in guinea pig myocytes. This might contribute to a superior antiarrhythmic efficacy as compared tod-Sotalol.

Keywords

potassium channel / delayed rectifier current / antiarrhythmia agents / cardiomyocytes / catecholamines

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