内皮素对慢性低氧大鼠肺动脉平滑肌细胞膜钾通道活性的影响  

Effect of endothelin-1 on voltage-gated K^+ current in the pulmonary artery smooth muscle cells of chronic hypoxic rats

作　　者：樊再雯[1] 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卫生部呼吸系疾病重点实验室,湖北武汉430030

出　　处：《药学学报》2005年第4期327-331,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(39970332)

摘　　要：目的　观察内皮素(ET 1)对慢性低氧大鼠肺动脉平滑肌细胞 (PASMCs)膜电压门控钾通道 (KV)活性的影响。方法　将 12只Wistar大鼠随机分为对照组和慢性低氧组,每组 6只。用全细胞膜片钳记录方法研究ET 1对两组大鼠PASMCs膜电位 (Em )、膜电容 (Cm )及电压门控钾电流 (IKV)的影响。结果　ET 1可引起两组大鼠PASMCs去极化,且对两组大鼠IKV均有明显的浓度依赖性抑制作用。在慢性低氧组,高浓度ET 1对IKV的抑制作用强于对照组。结论　低氧并未改变ET 1引起PASMCs去极化及浓度依赖性抑制IKV的特性,且慢性低氧可能改变了PASMCs对ET 1的敏感性,内皮素和低氧对PASMCsIKV的抑制作用有协同性。Aim To investigate the effect of endothelin-1 (ET-1) on voltage-gated K + current in the pulmonary artery smooth muscle cells (PASMCs) of chronic hypoxic rats. Methods Twelve male Wistar rats matched with age and body weight were randomly divided into control and chronic hypoxic groups. Single PASMCs were obtained with acute enzyme (collagnase plus papain) dispersing method. Using the whole cell patch clamp technique in freshly isolated PASMCs from normoxic and hypoxic rats, the effects of ET-1 on voltage-gated K + current were recorded. Results The resting membrane potential (E m) in PASMCs from chronic hypoxic rats was significantly depolarized to ( -32.6±1.3) mV compared with ( -42.1±2.8) mV in PASMCs from normoxic rats (P<0.01, n=20). In chronic hypoxic rats, the IK V was smaller than that in normotensive rats [+50 mV, the peak current density of control group reduced from (136±24) pA/pF to (98±12) pA/pF, percent inhibition was (28.4±2.4)%, P<0.01, n=6]. Application of ET-1 (1×10 -8 mol·L -1) also depolarized PASMCs of chronic hypoxic rats from ( -32.6±1.3) mV to (-21.5±1.7) mV (P<0.05, n=20) compared with the ET-1 induced depolarization from (-42.1±2.8) mV to (-22.6±1.4) mV (P<0.05, n=20). The change in membrane potential induced by ET-1 was not significantly different between PASMCs from normoxic and hypoxic rats. ET-1 (1×10 -10 to 1×10 -7 mol·L -1) caused concentration-dependent inhibition of K + current in PASMCs both from normoxic and hypoxic rats. At higher concentration (1×10 -8-1×10 -7 mol·L -1), the effect of ET-1 on K + current in PASMCs from hypoxic rats was greater than that of normoxic rats [ +50 mV, the peak current density of control group reduced from (136±24) pA/pF to (40±10) pA/pF, percent inhibition was (71±7)%, that of hypoxic group was (98±6) pA/pF to ( 16±3) pA/pF, percent inhibition was (85±10)% at 1×10 -7 mol·L -1, n=6, P<0.01]. Conclusion Chronic hypoxia did not change the effect of ET-1 on the p

关 键 词：钾通道 内皮素 膜片钳 慢性低氧 肺动脉平滑肌细胞 

分 类 号：R338[医药卫生—人体生理学] R965[医药卫生—基础医学]