Smirnov S V, Robertson T P, Ward J P, Aaronson P I
Smooth Muscle Research Group, United Medical School, Guy's Hospital, London, United Kingdom.
Am J Physiol. 1994 Jan;266(1 Pt 2):H365-70. doi: 10.1152/ajpheart.1994.266.1.H365.
Pulmonary hypertension due to long-term hypoxia occurs as a result of both chronic obstructive pulmonary disease and habitation at high altitudes. Studies in animal models of chronic hypoxia have demonstrated the development of a persistent depolarization of pulmonary artery (PA) smooth muscle cells (SMCs). In seeking to explain this effect, we compared under normoxic conditions the K+ currents in SMCs isolated from small PA of chronically hypoxic and normoxic rats. Chronic hypoxia was associated with a marked (40-50%) reduction in amplitude of a K+ current, which had the pharmacological and kinetic characteristics of a delayed rectifier. The resting potential of the isolated PA cells from chronically hypoxic animals was significantly more positive (-43.5 +/- 2 mV) than that of cells from normoxic animals (-54.3 +/- 2 mV), and this depolarization could be approximately mimicked in the cells from normoxic animals by application of 1 mM 4-aminopyridine, a blocker of the delayed rectifier K+ current. Glibenclamide (1 microM), a blocker of ATP-sensitive K+ (KATP) channels, also caused a substantial (14.5 +/- 2.2 mV) depolarization of the membrane. These results suggest that both delayed rectifier and ATP-dependent K+ currents contribute to setting the membrane potential in these cells and are consistent with the possibility that downregulation of the delayed rectifier K+ current contributes to the depolarization and altered responsiveness to vasoactive agents of PAs that occurs during long-term hypoxia.
长期缺氧所致的肺动脉高压是慢性阻塞性肺疾病和高海拔居住的结果。对慢性缺氧动物模型的研究表明，肺动脉（PA）平滑肌细胞（SMC）会出现持续性去极化。为了解释这种效应，我们在常氧条件下比较了从慢性缺氧大鼠和常氧大鼠的小肺动脉分离出的SMC中的钾离子电流。慢性缺氧与一种钾离子电流幅度显著降低（40 - 50%）有关，该电流具有延迟整流器的药理学和动力学特征。慢性缺氧动物分离出的PA细胞的静息电位（-43.5 ± 2 mV）比常氧动物细胞的静息电位（-54.3 ± 2 mV）明显更正，并且通过应用1 mM 4 - 氨基吡啶（一种延迟整流器钾离子电流的阻滞剂），常氧动物细胞中的这种去极化可被大致模拟。格列本脲（1 μM），一种ATP敏感性钾离子（KATP）通道的阻滞剂，也引起了细胞膜的显著去极化（14.5 ± 2.2 mV）。这些结果表明，延迟整流器和ATP依赖性钾离子电流都有助于设定这些细胞的膜电位，并且与延迟整流器钾离子电流下调导致长期缺氧期间PA去极化和对血管活性药物反应性改变的可能性一致。
