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慢激活延迟整流钾电流(slowly activated delayed rectifier potassium current,IKs)由KCNQ1通道与KCNE1通道共同编码。KCNQl或KCNEl通道电流功能上调能够引发短QT综合征。全新化学结构化合物QO-58对KCNQ1-5通道具有开放作用。该文采用电生理膜片钳技术探讨QO-58对KCNQl/KCNEl/IKs通道电流作用,观察QO-58的心脏电生理毒性。结果表明,化合物QO-58能够浓度依赖性地增大KCNQ1/KCNE1通道电流,并且引起KCNQ1/KCNE1通道电流电压关系曲线向超极化方向移动。QO-58能够轻微增大豚鼠心室肌IKs通道电流,但对豚鼠乳头肌动作电位时程无显著影响。结果提示,QO-58心脏电生理毒性较低,具有进一步研发成为治疗兴奋性增强等相关疾病的新型药物的潜力。
Slow activated delayed rectifier potassium current (IKs) is encoded by the KCNQ1 channel and the KCNE1 channel. Functional upregulation of KCNQ1 or KCNE1 channel currents can trigger short QT syndromes. The new chemical structure of the compound QO-58 on the KCNQ1-5 channel has an open effect. In this paper, electrophysiological patch clamp technique was used to investigate the effect of QO-58 on KCNQ1 / KCNEl / IKs channel currents, and to observe the cardiac electrophysiological toxicity of QO-58. The results showed that compound QO-58 could increase KCNQ1 / KCNE1 channel currents in a concentration-dependent manner and cause KCNQ1 / KCNE1 channel current-voltage curve to move toward hyperpolarization. QO-58 could slightly increase IKs channel currents in guinea pig ventricular myocytes, but had no significant effect on the duration of action potential of guinea pig papillary muscles. The results suggest that QO-58 cardiac electrophysiological toxicity is low, with further research and development as the treatment of excitability and other diseases related to the potential of new drugs.