摘要
目的 观察畦巴因和乌头碱对豚鼠和大鼠心肌单细胞离子通道的作用,确定两药诱发心律失常时离子靶点和最佳靶点,建立细胞水平的心律失常模型。方法 用全细胞膜片钳技术记录哇巴因和乌头碱对酶解法分离的豚鼠和大鼠心肌细胞离子通道的作用。结果 5;μmol·L^(-1)哇巴因使豚鼠心肌细胞APD延长、I_(Ca-L)增加、I_k减少、I_(k1)减少;1μmol·L^(-1)乌头碱使大鼠心肌细胞APD延长、I_(Ca-L)增加、I_(to)减少、I_(k1)增加。结论 哇巴因和乌头碱诱发心律失常的离子靶点有APD,I_(Ca-L),I_k,I_(to)和I_(k1)而最佳靶点应为APD,I_(Ca-L),I_k和I_(to)。在单细胞水平分别应用哇巴因和乌头碱诱发豚鼠和大鼠心律失常.具有稳定性高、条件可控、重复性好等优点,可用于药物筛选和机制研究。
Aim To observe the effects of ouabain and aconitine on APD and ion channels in isolated
guinea pig and rat ventricular myocytes; to elucidate the action mechanisms of these two drugs and set up new
arrhythmie models on cellular level. Methods In isolated ventricular myocytes of guinea pig and rat, the
effects of ouabain and aconitine on APD, I_(Ca-L), I_k,I_(to), and I_(kl) were observed using the whole cell patch clamp
technique. Results Ouabain (5 μmol·L^(-1)) obviously prolonged the APD_(90), increased I_(Ca-L), decreased I_k and
I_(kl) in guinea pig ventricular myocytes. Aconitine (1 μmol·L^(-1)) lengthened the APD_(90), increased I_(Ca-L), decreased I_(to) and increased I_(kl) in rat ventricular myoeytes. Conclusion The targets on ouabain- and aconitine-
induced arrbythmias included APD, I_(Ca-L), I_k, I_(to) and I_(kl). APD, I_(Ca-L), I_k and I_(to) must be the powerful ones,
both in arrhythmic and antiarrhythmic courses. The ouabain- and aeonitine- induced arrhythmic models on
cellular level were built to study the antiarrhythmie mechanisms of chemicals and evaluate new drugs. These two
new-type models in vitro were stable, liable, repeatable and economic, which were superior to those typical models in vivo.
出处
《药学学报》
CAS
CSCD
北大核心
2004年第5期328-332,共5页
Acta Pharmaceutica Sinica
基金
国家自然科学基金(39870922
30271599)
