cGMP对慢性低氧大鼠肺动脉平滑肌细胞膜电压门控钾通道的作用  

Effect of cGMP on voltage-gated potassium channel in pulmonary artery smooth muscle cells from rats exposed to chronic hypoxia

作　　者：张永昶[1] 倪望[1] 甄国华 张珍祥[1] 徐永健[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院呼吸内科,湖北武汉430030

出　　处：《中国病理生理杂志》2003年第8期1012-1015,共4页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目 (No .39970 332 )

摘　　要：目的 :探讨cGMP对慢性低氧大鼠肺动脉平滑肌细胞 (PASMC)膜电压门控钾通道 (Kv通道 )的作用 ,为进一步阐明慢性低氧性肺动脉高压的发病机理提供理论依据。方法 :Wistar大鼠 ,随机分为对照组和慢性低氧组 ,低氧组大鼠每天低氧 (氧浓度 10 %± 1% ) 8h ,连续 4周。单个大鼠PASMC的获得采用急性酶分离法 (胶原酶Ⅰ型和木瓜蛋白酶 )。采用全细胞膜片钳技术测定两组PASMC的静息膜电位 (Em)和电压门控钾通道的钾离子电流 (IKV) ,观察并比较cGMP (1mmol/L)以及cGMP和蛋白激酶G(PKG)抑制剂H - 8(1mmol/L)应用后两组PASMCIKV的不同变化。结果 :慢性低氧大鼠PASMC的静息膜电位和电压门控钾通道电流明显低于正常对照组。cGMP可抑制正常和慢性低氧大鼠PASMC +5 0mV刺激时的峰值IKV[正常组从 (118 0± 5 0 )pA/pF下降到 (89 9± 16 5 )pA/pF ,n =6 ,P<0 0 5 ;慢性低氧组则从 (81 0± 5 0 )pA/pF下降到 (5 6 8± 9 1)pA/pF ,n =6 ,P <0 0 5 ],该抑制作用可被PKG的抑制剂H - 8阻断 [正常组 (119 2± 10 3)pA/pFvs (117 8± 9 1)pA/pF ,n =6 ,P >0 0 5 ;慢性低氧组 (96 8± 6 2 )pA/pFvs(98 0± 2 2 )pA/pF ,n =6 ,P >0 0 5 ]。结论 :慢性低氧抑制肺动脉平滑肌细胞的电压门控钾通道。AIM: To investigate the effect of cGMP on voltage-gated potassium channel in pulmonary artery smooth muscle cells (PASMCs) from rats exposed to chronic hypoxia. METHODS: (1) Wistar rats were randomly divided into control group (group A) and chronic hypoxia group (group B). Then group B received hypoxia 8 hours per day for 4 consecutive weeks. (2) Single PASMC was obtained via acute enzyme separation method. (3) Conventional whole-cell patch clamp technique was used to record resting membrane potential (Em) and ion currents of voltage-gated potassium channel. The changes of ion currents of voltage-gated potassium channel before and after applying cGMP (1 mmol/L), an agonist of protein kinase G (PKG), and cGMP plus H-8 (1 mmol/L), an inhibitor of PKG were compared between two groups. RESULTS: The Em of group B were significantly lower than that of group A. The ion currents of voltage-gated potassium channel in group A and group B were all significantly inhibited by cGMP [control group: from (118.0±5.0) pA/pF to (89.9±16.5) pA/pF, n= 6, P< 0.05;chronic hypoxia group: from (81.0±5.0) pA/pF to (56.8±9.1) pA/pF, n= 6, P< 0.05]and these effects were reversed by H-8 [control group: from (119.2±10.3) pA/pF to (117.8±9.1) pA/pF, n= 6, P> 0.05;chronic hypoxia group: from (96.8±6.2) pA/pF to (98.0±2.2) pA/pF, n= 6, P> 0.05]. CONCLUSIONS: The currents of voltage-gated potassium channel was inhibited by chronic hypoxic. The inhibitory effect of cGMP on currents of voltage-gated potassium channel in PASMCs from both normal and chronic hypoxic rats may be probably through the phosphorylation of voltage-gated potassium channel.

关 键 词：胞苷环—磷酸 低氧 肺动脉 钾通道 

分 类 号：R363[医药卫生—病理学]