Role of membrane potential in hypoxic inhibition of L-arginine uptake by lung endothelial cells.
System y+ accounts for the majority of L-arginine transport by pulmonary artery endothelial cells (PAEC). Given that membrane potential is a driving force for transport via system y+, we examined the hypothesis that hypoxia inhibits this transport by decreasing membrane potential. Porcine PAEC or plasma membrane vesicles derived from these cells were exposed to normoxia (room air-5% CO2) or hypoxia (0% O2-95% N2-5% CO2). After exposure, L-[3H]arginine transport and/or accumulation of the lipophilic cation [3H]tetraphenylphosphonium, a quantitative sensor of changes in cell membrane potential, were measured. Hypoxia caused reversible time-dependent decrease in L-arginine transport and membrane potential in PAEC and in plasma membrane vesicles. Comparable decreases in membrane potential and L-arginine transport by PAEC were also observed after depolarization induced by KCl or ouabain. Hyperpolarization, 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 and L-arginine transport in PAEC. These results indicate that hypoxia-induced plasma membrane depolarization is responsible for reduced L-arginine transport by system y+ in hypoxic porcine PAEC.
Zharikov
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Department of Medicine, University of Florida College of Medicine, Gainesville, USA.
Herrera
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Block
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D000818:Animals; D001120:Arginine / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D000860:Hypoxia / Q000378:metabolism*; D008564:Membrane Potentials; D009861:Onium Compounds / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011652:Pulmonary Circulation; D012964:Sodium / Q000502:physiology; D013552:Swine; D014634:Valinomycin / Q000494:pharmacology
D009861:Onium Compounds; D009943:Organophosphorus Compounds; D014634:Valinomycin; D010042:Ouabain; D001120:Arginine; D012964:Sodium; D011188:Potassium; C013289:tetraphenylphosphonium