The role of membrane potential in hypoxic inhibition of l-arginine
uptake by lung endothelial cells.
Zharikov, S. I., H. Herrera, and E. R. Block.
Department of Medicine, University of Florida College of Medicine,
and the Medical Research Service, Veterans Affairs Medical Center,
Gainesville, FL 32608-1197
APStracts 3:0163L, 1996.
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, [3H]-L-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 decreases 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.
Received 9 July 1996; accepted in final form 4 September 1996.
APS Manuscript Number L211-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996