摘要
目的研究阿米洛利对甲状腺素诱发大鼠肥厚心肌瞬时外向钾电流(Ito)的作用,观察正常组、肥厚组及阿米洛利处理组心肌细胞Ito特性的不同,以阐明肥厚大鼠心肌细胞动作电位的变化及阿米洛利抗心肌肥厚的电生理机制。方法大鼠ipL-甲状腺素造成心肌肥厚模型后,用标准微电极技术记录大鼠右心室乳头状肌动作电位;用膜片钳技术记录大鼠单个心室肌细胞的Ito。结果肥厚大鼠心肌细胞动作电位时程(尤其是APD20)明显延长,阿米洛利可使过度延长的APD20恢复或接近于正常值。肥厚组心肌细胞Ito幅度和密度均增加,激活动力学特性无改变。Amiloride[0.5mg/(kg·d),p.o]能抑制Ito电流幅度及电流密度的增加。结论在甲状腺素诱发大鼠心肌肥厚模型中,Ito特性发生了变化,这是造成肥厚心肌电生理异常的离子基础。Amiloride能对抗甲状腺素致肥厚的心肌细胞Ito的变化,这可能与其抗心肌肥厚的作用有关。
[Objective] To investigate the differences of transient outward potassium current（Ito） in normal, thyroxine-induced hypertrophied and Amiloride-pretreated rat ventrieular myoeytes. [Methods] Myocardial hypertrophy was induced by ip L-Thyroxine in rats. Action potentials of papillary muscle in isolated myoeytes from rats were examined using standard and ion-selective mieroeleetrode techniques. The whole cell patch clamp technique was used to record ho. [Results] After administration of Thyroxine in rats, the morphology and duration of action potential of papillary muscle （especially to APD20,50,90） changed. At the dose of 0.5 mg/（kg·d）, Amiloride （p.o） was shown to prevent APD20 of hypertrophic papillary from prolongation. The currents （Ito） were larger in hypertrophied cells （571.5pA） than that in normal cells （374）. When Ito amplitude was related to the cell membrane area, as estimated by membrane capacitance measurement, there were significant differences in current density （4.37 vs 5.19pA/pF） in both normal and hypertrophied cells, respectively. Whereas ho revealed the same voltage dependence. The potential giving 50% of activation （V1/2） did not move in hypertrophied cells, neither did the slope of activation curve. 0.5 mg/（kg·d）, Amiloride （p.o） could inhibit the increase of amplitude and current density of ho. [Conclusion] In the model of thyroxine-induced hypertrophy, the properties of ho had changed a lot, which contributed to the eleetrophysiologie abnormalities in myocardial hypertrophy, Amiloride could be effective against changes of ho induced by Thyroxine, which participated its antihypertrophie effects.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2005年第17期2597-2601,共5页
China Journal of Modern Medicine
关键词
阿米洛利
心肌肥厚
膜片钳
瞬时外向钾电流
amiloride
myocardial hypertrophy
patch clamp
transient outward potassium current
