AJP - Cell Physiology, Vol 254, Issue 4 C526-C534, Copyright © 1988 by American Physiological Society
Lithium movements in resting and chemotactic factor-activated human neutrophils
L. Simchowitz
Department of Medicine, John Cochran Veterans Administration Medical Center, St. Louis, Missouri.
The ability of the chemotactic factor-activated Na+-H+ exchange system of
human neutrophils to bind and transport other cations of the alkali metal
series was investigated. After exposure of cells to the tripeptide
N-formyl-methionyl-leucyl-phenylalanine (FMLP), the influx of Li+ was
measured by flame photometry and correlated with changes in intracellular
pH (pHi) derived from the equilibrium distribution of
5,5-dimethyloxazolidine-2,4-dione. In Na+-depleted cells, Li+ (Km
approximately equal to 14 mM) could substitute effectively for Na+ (Km
approximately equal to 23 mM) at the external translocation site of the
carrier, though the maximal transport rate for Li+ (approximately 8
meq.l-1.min-1) was roughly half that for Na+ (approximately 15
meq.l-1.min-1). On the other hand, the carrier lacked appreciable affinity
for K+, Rb+, and Cs+. The influx of Li+ from the external solution was
accompanied by an equivalent counterefflux of H+ from the internal milieu.
The H+ efflux thus induced led to an intracellular alkalinization of
approximately 0.7 units, the pHi rising from approximately 7.20 to
approximately 7.90. The influx of Li+, as well as the increase in pHi in
140 mM Li+ medium, was competitively inhibited by amiloride (Ki
approximately equal to 9 microM). Extracellular H+ also behaved as a
competitive inhibitor of Li+ with a Ki of approximately 30 nM (pK'a
approximately 7.50). These studies indicate that the FMLP-activated alkali
metal cation-H+ exchange mechanism of neutrophils shares a number of
features in common with those of Na+-H+ exchangers in a variety of
different cells.
