BQ123对慢性缺氧大鼠肺动脉平滑肌细胞电压门控钾通道活性的影响

Effect of BQ123 on the voltage-gated K^+ current of pulmonary artery smooth muscle cells of rats exposed to chronic hypoxia

目的:探讨内皮素-1受体(ETA)拮抗剂BQ123对慢性缺氧大鼠肺动脉平滑肌细胞(PASMCs)电压门控钾通道(KV)活性的影响。方法:将12只Wistar大鼠随机分为对照组和慢性缺氧组,每组6只。用急性酶分离法(胶原酶+木瓜酶)获得单个PASMCs,用全细胞膜片钳记录方法,观察BQ123对2组大鼠PASMCs电压门控钾电流(IKV)的影响。结果:(1)在2组大鼠,ET-1(10-8mol·L-1)对PASMCs IKV都可产生抑制作用,+50 mV时的抑制率分别是(60.21±5.32)%和(71.04±6.58)%。(2)对照组大鼠,单独使用BQ123对PASMCs IKV无影响(P>0.05,n=5),在此基础上使用ET-1,ET-1对IKV的抑制作用依然存在。(3)慢性缺氧组大鼠,单独使用BQ123可增加PASMCs IKV,+50mV从(98.36±12.04)pA/pF至(105.76±12.13)pA/pF,但差异无显著(P>0.05,n=6),同时使用ET-1后发现BQ123可部分抵消ET-1对IKV的抑制作用,+50 mV从(28.49±6.69)pA/pF升至(74.19±9.74)pA/pF(P<0.01,n=6)。结论:常氧时,ET-1对IKV的抑制作用不是通过ETA介导的。但在缺氧条件下,ETA拮抗剂BQ123可部分拮抗ET-1对IKV的抑制作用,说明缺氧时ETA受体介导了ET-1对IKV抑制作用。

AIM： To study the effect of BQ123 on voltage - gated K^＋ current in pulmonary artery smooth muscle cells （PASMCs） from chronic hypoxic rats. METHODS： Twelve age and body weight matched Wistar rats were randomly divided into control and chronic hypoxic group. Single PASMCs were obtained with acute enzyme （collagnase I plus papain） dispersing method. Using the whole cell patch - clamp technique in freshly isolated PASMCs from normorxic and hypoxic rats, the effects of ET - 1 and BQ123, a selective ETA receptor antagonist, on voltage - gated K^＋ current were recorded. RESULTS： （1） ET - 1 （10^-8 mol · L^-1 ） caused inhibition of K^＋ current in PASMCs from normoxic and hypoxic rats. The effect of ET - 1 on K^＋ current in PASMCs from hypoxic rats was greater than that from normoxic rats [ ＋ 50 mV, percent inhibition were （71.04 ± 6. 58） % and （60. 21 ± 5.32） %, respectively, P 〈 0. 01, n = 6 ]. （2） In normoxic PASMCs, neither BQ123 alone produced influence on the IKv （P 〉 0. 05, n = 5 ） , nor ETA receptor blockade had change of ET- 1 mediated IKv inhibition. （3） In chronic hypoxic PASMCs, BQ123 significantly reduced the effect of ET - 1 mediated IKv inhibition, from （28. 49 ± 6. 69 ） pA/pF to （74. 19 ± 9. 74 ） pA/pF at ＋ 50 mV （ P 〈 0. 01, n = 6 ）. CONCLUSION： In normoxic condition, the effect of ET - 1 on IKv of PASMCs is not mediated by BQ123, a selective ETA receptor antagonist. During exposure to chronic hypoxia, the inhibition of ET - 1 on IKv of PASMCs is partly mediated by BQ123, namely, ETA receptor mediates the effect of ET - 1 on IKv of chronic hypoxic PASMCs.