延迟整流钾通道在哮喘大鼠模型气道平滑肌张力调控中的作用

The role of delayed rectifier potassium channels in the regulation of bronchial smooth muscle tension in asthmatic rats

目的 探讨电压依赖性延迟整流钾通道 (KV)在哮喘大鼠模型气道平滑肌张力调控中的作用及其对气道反应性的影响。方法 应用等长张力记录方法 ,观察钾通道对正常和哮喘大鼠离体支气管静息张力及收缩张力的影响。结果 (1)KV 阻断剂 4 氨基吡啶 (4 AP)诱发大鼠离体支气管产生浓度依赖性的收缩反应。哮喘组支气管 (10只 ) 4 AP收缩反应量效曲线较对照组 (10只 )明显左移 ,两者达到最大效应的一半所需浓度的负对数值 (pD2 )分别为 2 5 8± 0 0 7,2 12± 0 0 4,两组比较差异有显著性 (P <0 0 1) ;最大反应强度 (Emax)哮喘组为 (3 2± 5 )mg/mg ,与对照组 [(3 1± 6)mg/mg]比较 ,差异有显著性 (P >0 0 5 ) ;(2 )在对照组中 ,4 AP使支气管对内皮素 1(ET 1)和组胺的收缩反应量效曲线明显左移 ,处理前pD2 分别为 6 2 7± 0 3 8、5 5 9± 0 2 7,处理后为 6 80± 0 47、6 42± 0 14,处理前、后比较 ,差异有显著性 (P均 <0 0 1) ;Emax处理前分别为 (3 6± 8)mg/mg、(3 6± 8)mg/mg,处理后为(40± 8)mg/mg、(3 9± 9)mg/mg,处理前、后比较 ,差异有显著性 (P均 >0 0 5 ) ;(3 )在哮喘组中 ,4 AP对ET 1和组胺诱发支气管收缩反应的量效曲线无显著影响 ,处理前pD2 分别为 6 5 1± 0 0 7、5 86± 0 14。

Objective To investigate the role of delayed rectifier potassium channels(K V) in the regulation of bronchial smooth muscle tension in asthmatic rats and their effects on bronchial reactivity in vitro Methods By using a specific potassium channel blocker, the bronchial contraction induced by spasmogens was observed in normal and asthmatic rats with the isometric tension recording technique Results (1) K V blocker 4 aminopyridine (4 AP) caused concentration dependent bronchial contraction in vitro The concentration response curve to 4 AP in the asthmatic group showed a left displacement with bigger pD 2 (the negative logarithm of the drug concentration causing 50% of maximal effect,2 58±0 07, n =10, P <0 001) and no change in E max [maximal effect,(32±5) mg/mg, P >0 05],compared with pD 2 (2 12±0 04, n =10) and E max [(31±6) mg/mg] obtained in the control group; (2) In the control group,pre treatment with 0 1 mmol/L 4 AP displaced the concentration response curves to ET 1 and histamine to the left pD 2 (for ET 1 and histamine) before and after 4 AP treatment was 6 27±0 38,5 59±0 27 and 6 80±0 47,6 42±0 14 respectively ( P <0 01) E max before and after 4 AP treatment was (36±8) mg/mg,(36±8)mg/mg and (40±8) mg/mg,(39±9)mg/mg respectively( P >0 05); (3) In the asthmatic group,pre treatment with 0 1 mmol/L 4 AP had no effect on the concentration response curve to ET 1 and histamine There was no significant difference ( P >0 05) in pD 2 before (6 51±0 07,5 86±0 14 respectively) and after (6 48±0 16,5 96±0 08 respectively) 4 AP treatment,and in E max before [(61±8) mg/mg,(54±11) mg/mg respectively] and after [(65±10) mg/mg, (55±9) mg/mg respectively] 4 AP treatment Conclusion The activity of K V decreases in bronchial smooth muscle isolated from asthmatic rats compared with that obtained from normal ones This change may be involved in the bronchial hyperreactivity to some spasmogens in vitro in asthmatic rats