Renal epithelial cell growth can occur in absence of Na+-H+ exchanger activity

MATTHIAS MOHRMANN, HORACIO F. CANTIELLO, AND DENNIS A. AUSIELLO

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY

Año: 1987 p. 633 - 638

0363-6143

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-PK, 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-PK, 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 *Na+ 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.