ROLE OF MEMBRANE-POTENTIAL IN HYPOXIC INHIBITION OF L-ARGININE UPTAKEBY LUNG ENDOTHELIAL-CELLS

System y(+) accounts for the majority of L-arginine transport by pulmo nary artery endothelial cells (PAEC). Given that membrane potential is a driving force for transport via system y(+), we examined the hypoth esis that hypoxia inhibits this transport by decreasing membrane poten tial. Porcine PAEC or plasma membrane vesicles derived from these cell s were exposed to normoxia (room air-5% CO2) or hypoxia (0% O-2-95% N- 2-5% CO2). After exposure, L-[H-3]arginine transport and/or accumulati on of the lipophilic cation [3H]tetraphenylphosphonium, a quantitative sensor of changes in cell membrane potential, were measured. Hypoxia caused reversible time-dependent decreases in L-arginine transport and membrane potential in PAEC and in plasma membrane vesicles. Comparabl e decreases in membrane potential and L-arginine transport by PAEC wer e also observed after depolarization induced by KCl or ouabain. Hyperp olarization, induced by valinomycin, increased membrane potential and L-arginine transport in PAEC and plasma membrane vesicles. Valinomycin also prevented the hypoxia-mediated decreases in membrane potential a nd L-arginine transport in PAEC. These results indicate that hypoxia-i nduced plasma membrane depolarization is responsible for reduced L-arg inine transport by system y(+) in hypoxic porcine PAEC.