Osipenko O N, Alexander D, MacLean M R, Gurney A M
Department of Physiology & Pharmacology, University of Strathclyde, Royal College, Glasgow.
Br J Pharmacol. 1998 Aug;124(7):1335-7. doi: 10.1038/sj.bjp.0702006.
Exposing rats to chronic hypoxia increased the 4-aminopyridine (4-AP) sensitivity of pulmonary arteries. 1 mM 4-AP caused smooth muscle cell depolarization and contraction in arteries from hypoxic rats, but had little effect in age-matched controls. Chronic hypoxia downregulated delayed rectifier K+ current (IK(V)), which was nearly 50% blocked by 1 mM 4-AP, and non-inactivating K+ current (IK(N)), which was little affected by 1 mM 4-AP. The results suggest that IK(N) determines resting potential in control rats and that its downregulation following hypoxia leads to depolarization, which activates IK(V) and increases its contribution to resting potential. The hypoxia-induced increase in 4-AP sensitivity thus reflects a switch in the major K+ current determining resting potential, from IK(N) to IK(V). This has important implications for the actions and specificity of pulmonary vasodilator drugs.
将大鼠置于慢性低氧环境中会增加肺动脉对4-氨基吡啶（4-AP）的敏感性。1 mM 4-AP可使低氧大鼠动脉中的平滑肌细胞去极化并收缩，但对年龄匹配的对照组几乎没有影响。慢性低氧会下调延迟整流钾电流（IK(V)），该电流几乎被1 mM 4-AP阻断50%，以及非失活钾电流（IK(N)），该电流几乎不受1 mM 4-AP的影响。结果表明，IK(N)决定对照大鼠的静息电位，低氧后其下调导致去极化，进而激活IK(V)并增加其对静息电位的贡献。因此，低氧诱导的4-AP敏感性增加反映了决定静息电位的主要钾电流从IK(N)向IK(V)的转变。这对肺血管扩张药物的作用和特异性具有重要意义。
