钙激活钾/氯通道对大鼠逼尿肌不稳定调节作用的实验研究

Modulating effect of calcium activated potassium and chloride channels on detrusor instability

目的 研究钙激活钾 /氯通道对逼尿肌不稳定的调节作用的变化 ,探讨其在逼尿肌不稳定 (Detrusorinstability ,DI)发生中的作用。方法 采用Wistar大鼠DI模型 ,常规制备正常及DI逼尿肌条 ,体外张力测定其自发收缩频率和幅度 ,观察通道阻断剂及开放剂的作用。结果 DI组自发收缩频率与张力较对照组显著增加。大电导钙激活钾通道 (Bigcon ductancecalciumactivatedpotassiumchannel,BKca)阻断后 ,对照组频率降低而张力增加 ,DI组仅频率明显提高 ,开放后对照组频率与张力均降低 ,DI组仅频率明显下降。小电导钙激活钾通道 (Smallconductancecalciumactivatedpotassiumchannel,SKca)阻断后两组的频率与张力均明显增加 ,而开放后则对照组均降低 ,DI组仅频率下降。钾通道阻断或开放后对照组频率与张力的变化幅度明显高于DI组。钙激活氯通道 (Calciumactivatedchloridechannel ,Clca)阻断后 ,DI组频率与张力下降 ,而对照组无明显改变。结论 钙激活钾 /氯通道反馈调节逼尿肌的收缩 ,DI时Kca作用下调而Clca作用上调 。

Objective To study the modulation alterations of calcium activated potassium channel (Kca) and calcium activated chloride channels (Clca) on detrusor instability(DI) and their roles in DI. Methods The detrusor instability (DI) animal model was established using female Wistar rats. Detrusor strips were obtained from normal and DI rats. The contraction frequency and amplitude of the strips were measured by an in vitro tension test. The actions of channel openers and blockers were studied. Results Spontaneous contraction frequency and amplitude of DI increased significantly. The block of big conductance calcium activated potassium channel(Bkca) by Iberiotoxin resulted in decrease of frequency but increase of amplitude in the control, but only increase of frequency in DI. The opener, NS1619, resulted in decreases of frequency and amplitude in the control, but only decreases of frequency in DI. The block of small conductance Kca (Skca) by apamin resulted in increases of frequency and amplitude in both control and DI groups, but the opener, Chlorzoxazone, resulted in decreases of frequency and amplitude in the control, but only decrease of frequency in DI. The contraction alterations of DI were significantly lower than those of the control no matter Kca was blocked or opened. NFA, a selective Clca blocker, resulted in no significant frequency and amplitude alteration in the control, but significant decrease in DI. Conclusion These results suggested that Kca and Clca play a critical role in the modulation of detrusor contraction, and the down regulation of Kca and up regulation of Clca suggests that disorder of calcium related regulation may play an important role in DI.