新型ATP敏感性钾通道开放剂Iptakalim对慢性缺氧大鼠肺内动脉平滑肌细胞钾电流的影响  

Effects of iptakalim, a novel KATP opener, on potassium currents in intra-pulmonary artery smooth muscles derived from chronic hypoxic rats

作　　者：王虹[1] 解卫平[1] 齐栩[1] 汪海[2] 胡刚[3] 

机构地区：[1]南京医科大学第一附属医院呼吸内科,210029 [2]军事医学科学院毒物药物研究所,北京100850 [3]南京医科大学药理系,210029

出　　处：《国际呼吸杂志》2007年第9期641-645,共5页International Journal of Respiration

基　　金：国家创新药物基础研究重大项目基金（编号：969010101）;江苏省自然科学基金（编号：BK2006246）

摘　　要：目的探讨慢性缺氧对大鼠肺内动脉平滑肌细胞外向性钾电流的影响,及新型ATP敏感性钾（KATP）通道开放剂Iptakalim对此时钾电流的作用。方法SD雄性大鼠28只随机分成正常组、缺氧组[O2（10±0.5）%]、低剂量治疗组（每日缺氧前30min Iptakalim0.75mg·kg^-1灌胃）、高剂量治疗组（每日缺氧前30min Iptakalim1.5mg·kg^-1灌胃）,将缺氧组和已灌胃的大鼠放入常压缺氧舱制作动物模型。4周后,急性分离大鼠动脉平滑肌细胞,用膜片钳全细胞记录技术记录细胞外向性钾电流;通过浴槽内给药,观察Iptakalim对钾电流的影响。结果Iptakalim0.1,1,10,100μmol/L呈浓度依赖性增加正常大鼠肺内动脉平滑肌外向钾电流,格列本脲30μmol/L可拮抗Iptakalim10μmol/L对钾电流的增强作用;与对照组大鼠相比,慢性缺氧大鼠肺内动脉平滑肌细胞钾电流下降,电流密度减小（690±450）pA/pFvs（420±250）pA/pF（P〈0.01）,膜电容增大到（4.29±1.78）pF（P〈0.01）,电流-电压（I-V）曲线下移;与缺血氧组相比,每日缺氧前口服Iptakalim,细胞膜电容减小为（3.09±1.71）（P〈0.01）,电流密度增大到（610±320）pA/pF（P〈0.01）。结论慢性缺氧抑制大鼠肺内动脉平滑肌细胞钾通道,灌服Iptakalim可拮抗慢性缺氧对KATP通道的抑制作用。Objective To investigate effects of iptakalim,a novel KATP opener, on potassium currents in intra-pulmonary artery smooth muscles derived from chronic hypoxic rats. Methods Sprague-Dawley（SD） male rats were randomly divided into control group,chronic hypoxia group,treated Ⅰ group （chronic hypoxia and 0.75 mg·kg^-1·d^-1）,and treated Ⅱ group（chronic hypoxia and 1.5 mg·kg^-1·d^ -1）. Except the first group,the other three groups were put into hypoxic and normobaric chamber[（10±0.5）% O2,8 h·day^-1 and 6 day·week^-1 ] to establish rat models with chronic hypoxic pulmonary hypertension. Four weeks later,the effect s of iptakalim on potassium currents in intra-pulmonary arterial smooth muscle cells derived from rat were explored by using patch clamp technique （whole cell recording） after application of the drug in the bath. Results At 5 minutes after application of iptakalim at the concentrations of 0.1,1,10,100 μmol/ L, the potassium current amplitude in intra-pulmonary arterial SMC was enhanced in a concentration-dependent manner. The effects of iptakalim （10 μmol/L） on potassium current were blocked by glibenclamide （30 μmol/L）. The mean K^＋ current density-voltage relationship （I-V） curve in intra-pulmonary arterial SMC derived from hypoxia group rats shifted downward, compared with those from control rats. The membrane capacitance in the cells from simple hypoxic rats was increased （4.29±1.78 pF vs 3.16±1.86 pF, P〈0.05）,while the average current density was decreased（420±250 vs 690±450, P〈0.05） , compared with the cells from control rats. However, the values of membrane capacitance and K^＋ current density in the cells from the hypoxic rats pretreated with 4 weeks＇ iptakalim intake at the dosage of 0. 75 mg·kg^-1·d^-1 were close to those in control group. Conclusions The outward potassium currents in intra-pulmonary artery smooth muscle cells derived from rats could be enhanced by iptakalim, which could be blocked by glybenclimade,a specific KATP b

关 键 词：ATP敏感性钾通道 IPTAKALIM 肺内动脉平滑肌细胞 慢性缺氧 钾电流 

分 类 号：R54[医药卫生—心血管疾病]