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

Abstract

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 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.

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