Effect of normoxia and hypoxia on K⁺ current and resting membrane potential of fetal rabbit pulmonary artery smooth muscle

At birth, the increase in O₂ tension (pO₂) is an important cause of the decrease in pulmonary vascular resistance. In adult animals there are impressive interspecies differences in the level of hypoxia required to elicit a pulmonary vasoconstrictor response and in the amplitude of the response. Hypoxic inhibition of some potassium (K⁺) channels in the membrane of pulmonary arterial smooth muscle cells (PASMCs) helps to initiate hypoxic pulmonary vasoconstriction. To determine the effect of the change in pO₂ on fetal rabbit PASMCs and to investigate possible species-dependent differences, we measured the current-voltage relationship and the resting membrane potential, in PASMCs from fetal resistance arteries using the amphotericin-perforated patch-clamp technique under hypoxic and normoxic conditions. Under hypoxic conditions, the K⁺ current in PASMCs was small, and could be inhibited by 4-aminopyridine, iberiotoxin and glibenclamide, reflecting contributions by Kv, K_Ca and K_ATP channels. The average resting membrane potential was -44.3±1.3 mV (n=29) and could be depolarized by 4-AP (5 mM) and ITX (100 nM) but not by glibenclamide (10 μM). Changing from hypoxia, that mimicked fetal life, to normoxia dramatically increased the K_Ca and consequently hyperpolarized (-9.3±1.7 mV; n=8) fetal rabbit PASMCs. Under normoxic conditions K ⁺ current was reduced by 4-AP with a significant change in resting membrane potential (11.1±1.7 mV; n=8). We conclude that resting membrane potential in fetal rabbit PASMCs under both hypoxic and normoxic conditions depends on both Kv and K_Ca channels, in contrast to fetal lamb or porcine PASMCs. Potential species differences in the K⁺ channels that control resting membrane potential must be taken into consideration in the interpretation of studies of neonatal pulmonary vascular reactivity to changes in O₂ tension.