AJP - Cell Physiology, Vol 253, Issue 5 C633-C638, Copyright © 1987 by American Physiological Society
Renal epithelial cell growth can occur in absence of Na+-H+ exchanger activity
M. Mohrmann, H. F. Cantiello and D. A. Ausiello
Department of Medicine, Massachusetts General Hospital, Boston.
An electroneutral Na+-H+ exchange system has been described in a variety of
tissues and cell types, including those of renal origin, and has been
proposed to play a role in the activation of growth. We have recently
characterized the presence of this ubiquitous transporter in the apical
domain of confluent epithelial LLC-PK1 cells (J. Biol. Chem. 261:
3252-3258, 1986). Because most apical membrane proteins appear late in cell
growth, accompanying epithelial cell polarization, we determined whether
the Na+-H+ exchanger is required for the growth of LLC-PK1 cells. The
studies reported here show that there is no obligatory requirement for
increased H+ efflux or Na+ entry via the Na+-H+ exchanger for the
initiation of cell growth in this epithelial cell line. We used 22Na+
influx, acid extrusion, and intracellular pH determinations to show that
onset of cell growth, as measured by DNA content, precedes the activity of
the Na+-H+ exchanger in exponentially growing cells, whereas confluent
monolayers express Na+-H+ exchanger activity. When confluent cells are
replated at low density, Na+-H+ exchanger activity disappears within 8 h in
contrast to high-density replated cells. The fact that Na+-H+ exchanger
activity is only present in confluent monolayers suggests that the
development of tight junctions and polar differentiation play a role in the
expression of the Na+-H+ exchanger and that this exchanger is more
important to the polar epithelial cell for transepithelial transport than
for the maintenance of intracellular pH.
