Dukes I D, Morad M
Department of Physiology, University of Pennsylvania, Philadelphia 19104-6085.
Am J Physiol. 1989 Nov;257(5 Pt 2):H1746-9. doi: 10.1152/ajpheart.1989.257.5.H1746.
The action of tedisamil, a new bradycardiac agent with antiarrhythmic properties, was investigated in single rat ventricular myocytes using the whole cell voltage-clamp technique. Under current clamp conditions, 1-20 microM tedisamil caused marked prolongations of the action potential. Over the same concentration range, in voltage-clamped myocytes, tedisamil suppressed the transient outward current (ito) and enhanced its inactivation in a dose-dependent manner. The half-maximal dose for the effect of tedisamil on ito was approximately 6 microM. Tedisamil had no significant effects on the inwardly rectifying potassium current and calcium current but did suppress the sodium current at concentrations greater than 20 microM. Our findings suggest that tedisamil represents a new type of antiarrhythmic agent that primarily suppresses the transient outward K+ current.
采用全细胞电压钳技术，在单个大鼠心室肌细胞中研究了具有抗心律失常特性的新型心动过缓药物替地沙米的作用。在电流钳制条件下，1-20微摩尔的替地沙米可使动作电位显著延长。在相同浓度范围内，在电压钳制的肌细胞中，替地沙米以剂量依赖的方式抑制瞬时外向电流（ito）并增强其失活。替地沙米对ito作用的半数最大剂量约为6微摩尔。替地沙米对内向整流钾电流和钙电流无明显影响，但在浓度大于20微摩尔时可抑制钠电流。我们的研究结果表明，替地沙米是一种新型抗心律失常药物，主要抑制瞬时外向钾电流。
