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, ...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 result in its supperior antiarrhythmic efficacy compared to d sotalol.展开更多
To study the electrophysiologic effects of endothelin-1 (ET-1), we used patch clamp and glass microelectrode techniques to investigate the effects of ET-1 on cardiac L-Ica, Ik and Ik2 in guinea pig ventricular myocyte...To study the electrophysiologic effects of endothelin-1 (ET-1), we used patch clamp and glass microelectrode techniques to investigate the effects of ET-1 on cardiac L-Ica, Ik and Ik2 in guinea pig ventricular myocytes. The prolongation of APD50, was induced and EADs was triggered by 50 nM ET-1 perfusion. L-lea and Ik were enhanced by various ET-1 concentration from 1 to 50 nM with dose-dependence. Their steady-state activations of L-Iea and Ik shifted left with ET-1 concentration increments. ET-1 elicited a kind of GTP- dependent inward rectifier K current having a mean conductance of 82.36±1.27 pS. The open time and close time ( both interburst intervals and burst durations ) abbreviated with ET-1 concentration increase. The results suggested that EADs -ET evoked was ascribed to the prolongation on the plateau level, which resulted from L-Ica inhancement. The ET- evoked inward rectifier K+ current should be further studied.展开更多
文摘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 result in its supperior antiarrhythmic efficacy compared to d sotalol.
文摘To study the electrophysiologic effects of endothelin-1 (ET-1), we used patch clamp and glass microelectrode techniques to investigate the effects of ET-1 on cardiac L-Ica, Ik and Ik2 in guinea pig ventricular myocytes. The prolongation of APD50, was induced and EADs was triggered by 50 nM ET-1 perfusion. L-lea and Ik were enhanced by various ET-1 concentration from 1 to 50 nM with dose-dependence. Their steady-state activations of L-Iea and Ik shifted left with ET-1 concentration increments. ET-1 elicited a kind of GTP- dependent inward rectifier K current having a mean conductance of 82.36±1.27 pS. The open time and close time ( both interburst intervals and burst durations ) abbreviated with ET-1 concentration increase. The results suggested that EADs -ET evoked was ascribed to the prolongation on the plateau level, which resulted from L-Ica inhancement. The ET- evoked inward rectifier K+ current should be further studied.
