Sanguinetti M C
Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
Hypertension. 1992 Mar;19(3):228-36. doi: 10.1161/01.hyp.19.3.228.
Agents that modulate cardiac and smooth muscle K+ channels have stimulated considerable interest in recent years because of their therapeutic potential in a number of cardiovascular diseases. Foremost among these drugs are the so-called Class III antiarrhythmic agents, which act by prolonging cardiac action potentials, and K+ channel openers, which hyperpolarize and thereby relax smooth muscle cells. Many of the newly developed Class III antiarrhythmic agents probably act by specific block of one subtype of delayed rectifier K+ current, IKr, whereas other agents block more than one type of cardiac K+ current. Much controversy exists over the specific type of K+ channel (or channels) in smooth muscle that are activated by the K+ channel openers. Both groups of K+ channel modulators have great therapeutic promise, but the Class III antiarrhythmic agents may suffer from a side-effect that is directly linked to their specific mechanism of action.
近年来,调节心脏和平滑肌钾通道的药物因其在多种心血管疾病中的治疗潜力而备受关注。其中最重要的药物是所谓的Ⅲ类抗心律失常药物,其作用机制是延长心脏动作电位,以及钾通道开放剂,后者可使平滑肌细胞超极化从而舒张。许多新开发的Ⅲ类抗心律失常药物可能通过特异性阻断延迟整流钾电流的一种亚型IKr起作用,而其他药物则阻断多种类型的心脏钾电流。钾通道开放剂激活的平滑肌中特定类型的钾通道存在很多争议。这两类钾通道调节剂都有很大的治疗前景,但Ⅲ类抗心律失常药物可能存在与其特定作用机制直接相关的副作用。