The aim of this study was to compare the effects of d, l-Sotalol and dSotalol on the delayed rectifier K+ outward current in the presence of isoproterenol at different concentrations. Time-dependent delayed rectifier...The aim of this study was to compare the effects of d, l-Sotalol and dSotalol 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^(9)mol/L - 10^(-6) mol/L ), and isoproterenol (10^(-9)mol/L - 10^(-6)mol/L ) plus either d, l-Sotalol (10^(-4) mol/L) or d-Sotalol (10^(-4) mol/L)]. IK tail currents were measured upon repolarization to -40 mV. It was found that Ik was significantly amplified in the presence. of isoproterenol (10^(-9) mol/L- 10^(-6) mol/L) plus d-Sotalol. At 10-8 mol/L isoproterenol, Ik was increased by 92. 7%±17. 1 % (P<0. 05) and 54. 3 %±13. 4 % after d-Sotalol addition (P<0. 05). In contrast, d, l-Sotalol completely conteracted the increase of iK by isoproterenol (<10^(-8) mol/L), and compared to control, Ic was decreased by 35. 6 % ±8. 1% at 10^(-8) mol/L isoproterenol plus d, l-Sotalol (P<0. 05). It is concluded that the β-adrenergic blocking property of d, l-Sotalol but not that of dSotalol 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 to d-Sotalol.展开更多
文摘The aim of this study was to compare the effects of d, l-Sotalol and dSotalol 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^(9)mol/L - 10^(-6) mol/L ), and isoproterenol (10^(-9)mol/L - 10^(-6)mol/L ) plus either d, l-Sotalol (10^(-4) mol/L) or d-Sotalol (10^(-4) mol/L)]. IK tail currents were measured upon repolarization to -40 mV. It was found that Ik was significantly amplified in the presence. of isoproterenol (10^(-9) mol/L- 10^(-6) mol/L) plus d-Sotalol. At 10-8 mol/L isoproterenol, Ik was increased by 92. 7%±17. 1 % (P<0. 05) and 54. 3 %±13. 4 % after d-Sotalol addition (P<0. 05). In contrast, d, l-Sotalol completely conteracted the increase of iK by isoproterenol (<10^(-8) mol/L), and compared to control, Ic was decreased by 35. 6 % ±8. 1% at 10^(-8) mol/L isoproterenol plus d, l-Sotalol (P<0. 05). It is concluded that the β-adrenergic blocking property of d, l-Sotalol but not that of dSotalol 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 to d-Sotalol.
