Influence of chronic hypoxia on the contributions of non‐inactivating and delayed rectifier K currents to the resting potential and tone of rat pulmonary artery smooth muscle

Exposing rats to chronic hypoxia increased the 4‐aminopyridine (4‐AP) sensitivity of pulmonary arteries. 1 m m 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 ( I K(V) ), which was nearly 50% blocked by 1 m m 4‐AP, and non‐inactivating K + current ( I K(N) ), which was little affected by 1 m m 4‐AP. The results suggest that I K(N) determines resting potential in control rats and that its downregulation following hypoxia leads to depolarization, which activates I K(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 I K(N) to I K(V) . This has important implications for the actions and specificity of pulmonary vasodilator drugs. British Journal of Pharmacology (1998) 124 , 1335–1337; doi: 10.1038/sj.bjp.0702006