Differential effects of d,l-sotalol and d-sotalol on isoproterenol increased delayed rectifier outward potassium current in guinea pig myocytes  

作　　者：X.Z. Yao, N.C. Yannoulis, J.Kiehn and J.Brachmann 

出　　处：《Chinese Medical Journal》1997年第12期51-51,共1页中华医学杂志（英文版）

摘　　要：Objective Catecholamines antagonize the clinical efficacy of pure class Ⅲ antiarrhythmic agents in vivo. The antiarrhythmic agent d, l sotalol has β adrenergic blocking properties and class Ⅲ activity. However, its d isomer without β blockade has been shown to exert significant proarrhythmia. To determine the role of β adrenergic blocking properties of d, l sotalol on its antiarrhythmic effect, we compared the effects of d, l sotalol and d sotalol on delayed rectifier K + outward current in the presence of isoproterenol at different concentrations. Methods Time dependent delayed rectifier K + outward currents, I K (I Kr and I Ks ) and tail current (I K tail ) were measured in isolated guinea pig 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 Department of Cardiology, University Hospital Heidelberg, Germany (Yao XZ, Yannoulis NC, Kiehn J and Brachmann J) 40 mV in three experimental protocols [control, isoproterenol (10 9 -10 6 mol/L), and isoproterenol (10 9 -10 6 mol/L) plus either d, l sotalol (10 4 mol/L) or d sotalol (10 4 mol/L)]. I K tail currents were measured upon repolarization to 40 mV. Results Isoproterenol significantly inreased I K and I K tail in a concentration dependent manner. I K was significantly amplified in the presence of isoproterenol (10 9 -10 6 mol/L) plus d sotalol. At 10 8 mol/L isoproterenol, I K was increased by 92.3%±23.7% before and 54.3%±13.4% after d sotalol. In contrast, d, l sotalol strongly suppressed the effect of isoproterenol on I K, and compared to control, I K was decreased by 35.6%±8.1% at 10 8 mol/L isoproterenol. Conclusions The β adrenergic blocking property of d, l sotalol maintains delayed rectifier K + outward current block in the presence of isoproterenol in guinea pig myocytes. This may Objective Catecholamines antagonize the clinical efficacy of pure class Ⅲ antiarrhythmic agents in vivo. The antiarrhythmic agent d, l sotalol has β adrenergic blocking properties and class Ⅲ activity. However, its d isomer without β blockade has been shown to exert significant proarrhythmia. To determine the role of β adrenergic blocking properties of d, l sotalol on its antiarrhythmic effect, we compared the effects of d, l sotalol and d sotalol on delayed rectifier K + outward current in the presence of isoproterenol at different concentrations. Methods Time dependent delayed rectifier K + outward currents, I K (I Kr and I Ks ) and tail current (I K tail ) were measured in isolated guinea pig 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 Department of Cardiology, University Hospital Heidelberg, Germany (Yao XZ, Yannoulis NC, Kiehn J and Brachmann J) 40 mV in three experimental protocols [control, isoproterenol (10 9 -10 6 mol/L), and isoproterenol (10 9 -10 6 mol/L) plus either d, l sotalol (10 4 mol/L) or d sotalol (10 4 mol/L)]. I K tail currents were measured upon repolarization to 40 mV. Results Isoproterenol significantly inreased I K and I K tail in a concentration dependent manner. I K was significantly amplified in the presence of isoproterenol (10 9 -10 6 mol/L) plus d sotalol. At 10 8 mol/L isoproterenol, I K was increased by 92.3%±23.7% before and 54.3%±13.4% after d sotalol. In contrast, d, l sotalol strongly suppressed the effect of isoproterenol on I K, and compared to control, I K was decreased by 35.6%±8.1% at 10 8 mol/L isoproterenol. Conclusions The β adrenergic blocking property of d, l sotalol maintains delayed rectifier K + outward current block in the presence of isoproterenol in guinea pig myocytes. This may

关 键 词：Differential effects of d l-sotalol and d-sotalol on isoproterenol increased delayed rectifier outward potassium current in guinea pig myocytes 

分 类 号：R[医药卫生]