RELATIONSHIP BETWEEN MEMBRANE-POTENTIAL, DELAYED RECTIFIER K+ CURRENTS AND HYPOXIA IN RAT PULMONARY ARTERIAL MYOCYTES

Pulmonary arteries constrict in response to hypoxia, a process thought to involve oxygen sensing by K+ channels. We therefore investigated t he effects of hypoxia an voltage-activated K+ currents in myocytes iso lated from rat small pulmonary arteries using the patch-clamp recordin g technique. Experiments with iberiotoxin and intracellularly applied Ca2+ chelating agents revealed that hypoxia (P-O2, 20-30 mmHg; through out) inhibited the Ca2+-insensitive component of the delayed voltage-a ctivated outward K+ current. Hypoxia did not affect the membrane poten tial of these cells until they were depolarized by extracellular appli cation of 20 mM K+ current injection or endothelin-l. Hypoxia caused l ittle depolarization in the presence of prostaglandin F-2 alpha, an ag onist which was ineffective at inducing depolarization. These results suggest that an initial 'priming' depolarization may confer a sensitiv ity to hypoxia by activating delayed rectifier (K-V) channels. Once ac tive, these channels can then be closed by hypoxia, leading to further depolarization. It is unlikely therefore, that K-V channels are invol ved in controlling the resting membrane potential of these cells.