异丙托溴铵对慢性缺氧大鼠气管平滑肌细胞钙激活钾通道的作用

Effect of ipratropinum bromide on calcium activated potassium channel in tracheal smooth muscle cells from chronically hypoxic rats

目的 研究异丙托溴铵 (商品名 :溴化异丙托品 )对慢性缺氧大鼠气管平滑肌细胞大电导钙激活钾通道 (BKCa)的作用。方法 60只大鼠随机建立慢性大鼠缺氧模型组和正常组。急性分离单个大鼠气管平滑肌细胞。以膜片钳技术的内面向外式记录单通道电流。结果 (1 )采用内面向外式记录电流 ,慢性缺氧组通道开放概率 (P0 ,0 1 7± 0 0 7)与正常对照组 (0 35± 0 1 0 )比较 ,差异有显著性 (P <0 0 1 )。正常对照组快开放时间 (τO1 )为 (1 49± 0 41 )ms ,慢性缺氧组为 (0 53± 0 2 3)ms,正常对照组慢开放时间 (τO2 )为 (1 1 9± 3 2 )ms,慢性缺氧组为 (3 8± 1 4)ms,正常对照组快关闭时间(τc1 )为 (2 7± 0 9)ms,慢性缺氧组为 (5 7± 1 5)ms;正常对照组慢关闭时间 (τc2 )为 (1 2 1± 2 3)ms,慢性缺氧组为 (1 9 4± 2 9)ms ,两组快、慢、开、关闭时间比较差异有显著性 (P <0 0 1 )。异丙托溴铵与沙丁胺醇可逆转慢性缺氧对BKCa通道的抑制作用。通道的P0 慢性缺氧组为 0 1 5± 0 0 4、对照组为0 2 8± 0 0 9、沙丁胺醇组为 0 30± 0 0 8,三组间P0 比较差异有显著性 (P <0 0 1 )。慢性缺氧组τO1 、τO2 、τc1 和τc2 分别为 (0 55± 0 2 4 )ms、(3 6± 1 4)ms、(6 1± 1 6)ms、

Objective To study the effects of ipratropinum bromide on large conductance calcium activated potassium (BK Ca ) channel in tracheal smooth muscle cells (TSMC) from chronically hypoxic rat Methods The chronically hypoxic rat model was established Single TSMC was acutely isolated.Single channel currents were recorded by using the patch clamp technique in inside out configuration Results (1) Chronic hypoxia decreased BK Ca channel activity significantly in inside out recording Channel open probability (P 0) of BK Ca channel in the chronically hypoxic rats reduced significantly compared with that in the control rats(0 17±0 07 for the hypoxia, 0 35±0 10 for the control, n =30, t =8 22, P <0 01).Channel open time constants were significantly shortened in the chronically hypoxic group The fast and slow open time constants (τ O1 ,τ O2 )were significantly different from those in the control [τ O1 (1 49±0 41) ms, (0 53±0 23) ms, respectively, n =30, t =12 07, P <0 01;τ O2 (11 9±3 2) ms, (3 8±1 4) ms, respectively, n =30, t =12 60, P <0 01].Closing time prolonged significantly The fast and slow closing time constants (τ c1 ,τ c2 ) were significantly different from those in the control [τ c1 (2 7±0 9) ms, (5 7±1 5) ms, respectively, n =30, t =8 71, P <0 01; τ c2 (12 1±2 3) ms ,(19 4±2 9) ms, respectively, n =30, t =14 05, P <0 01] Ipratropinum bromide and salbutamol reversed the effect of chronic hypoxia on BK Ca channel P 0 increased, τ O1 and τ O2 were prolonged significantly τ c1 and τ c2 were shortened [P 0,0 15±0 04, 0 28±0 09, 0 30±0 08, respectively, n =25, F =39 90, P <0 01;τ O1 (0 55±0 24) ms, (0 89±0 25) ms, (1 03±0 33) ms, respectively, n =25, F =15 32, P <0 01;τ O2 (3 6±1 4) ms, (6 3±1 9) ms,(6 9±2 0) ms, respectively, n =25, F =40 10, P <0 01;τ c1 (6 1±1 6) ms, (3 3±1 2) ms, (3 0±0 8) ms,respectively, n =25, F =57 14, P <0 01;τ c2 (20 1±2 5) ms, (12 4±2 6) ms, (13 0±2 0) ms,respectively, n =25, F =24 60, P <0 01].Conclusion Chronic hypoxia decreased BK Ca channel activity.Ipratropinum bromide and salbutamol reversed the effect of chronic hypoxia on BK Ca channel The relaxing effect of ipratropinum bromide and salbutamol on TSMC may be partly mediated via activation of BK Ca channel