INFLUENCE OF CHRONIC HYPOXIA ON THE CONTRIBUTIONS OF NONINACTIVATING 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 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 (I-K(V)), which was nearly 50% blocked by 1 mM 4-AP, and non-inactivating K+ current (I-K(N)), which was little affected by 1 mM 4-AP. The results suggest that I-K(N) determines res ting potential in control rats and that its downregulation following h ypoxia leads to depolarization, which activates I-K(V) and increases i ts contribution to resting potential. The hypoxia-induced increase in 4-AP sensitivity thus reflects a switch in the major K+ current determ ining resting potential, from I-K(N) to I-K(V). This has important imp lications for the actions and specificity of pulmonary vasodilator dru gs.