Liu Xian-sheng, Xu Yong-jian, Zhang Zhen-xiang, Li Chao-qian, Yang Dan-lei
Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2003 Jan;26(1):18-21.
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.
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.
(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.
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.
探讨延迟整流钾通道（K(V)）在哮喘大鼠支气管平滑肌张力调节中的作用及其对体外支气管反应性的影响。
采用特异性钾通道阻滞剂，运用等长张力记录技术观察正常及哮喘大鼠中由致痉剂诱导的支气管收缩情况。
（1）K(V)阻滞剂4-氨基吡啶（4-AP）在体外引起浓度依赖性支气管收缩。与对照组的pD(2)（2.12±0.04，n = 10）和E(max) [最大效应，(31±6) mg/mg]相比，哮喘组对4-AP的浓度-反应曲线向左移位，pD(2)更大（引起最大效应50%的药物浓度的负对数，2.58±0.07，n = 10，P < 0.001），而E(max)无变化[最大效应，(32±5) mg/mg，P > 0.05]；（2）在对照组中，用0.1 mmol/L 4-AP预处理使对ET-1和组胺的浓度-反应曲线向左移位。4-AP处理前后ET-1和组胺的pD(2)分别为6.27±0.38、5.59±0.27和6.80±0.47、6.42±0.14（P < 0.01）。4-AP处理前后E(max)分别为(36±8) mg/mg、(36±8) mg/mg和(40±8) mg/mg、(39±9) mg/mg（P > 0.05）；（3）在哮喘组中，用0.1 mmol/L 4-AP预处理对ET-1和组胺的浓度-反应曲线无影响。4-AP处理前后pD(2)（分别为6.51±0.07、5.86±0.14和6.48±0.16、5.96±0.08）及E(max)（分别为[(61±8) mg/mg、(54±11) mg/mg和(65±10) mg/mg、(55±9) mg/mg]）均无显著差异（P > 0.05）。
与正常大鼠分离的支气管平滑肌相比，哮喘大鼠分离的支气管平滑肌中K(V)活性降低。这种变化可能参与了哮喘大鼠体外对某些致痉剂的支气管高反应性。
