AJP - Renal Physiology, Vol 263, Issue 1 83-F88, Copyright © 1992 by American Physiological Society

ARTICLES

Effects of chronic metabolic acidosis on Na(+)-H+ exchangers in LLC-PK1 renal epithelial cells

P. Igarashi, M. I. Freed, M. B. Ganz and R. F. Reilly
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.

Porcine renal epithelial cells (LLC-PK1/clone 4) have Na(+)-H+ exchangers with different kinetic properties in their apical and basolateral membranes. cDNAs encoding the basolateral Na(+)-H+ exchanger were recently cloned. To determine whether expression of the basolateral Na(+)-H+ exchanger was affected by chronic metabolic acidosis, LLC-PK1/clone 4 cells were grown on permeant supports and incubated in control medium (pH 7.4) or acid medium (pH 6.9). After 48 h, Na(+)-H+ exchanger transport activity was measured as N-ethyl-N-isopropylamiloride (EIPA)-sensitive 22Na+ influx. Acidification caused an 84% stimulation of the transport activity of the basolateral Na(+)-H+ exchanger. The apical Na(+)-H+ exchanger was stimulated 72%, and there was no change in the EIPA-insensitive 22Na+ flux across either membrane. Stimulation of Na(+)-H+ exchange was not due to differences in intracellular pH at the time transport was assayed. To determine whether there were corresponding changes in transcript levels, poly(A)+ RNA was isolated from LLC-PK1 cells and hybridized with a cDNA encoding the basolateral Na(+)-H+ exchanger. Levels of transcripts encoding the basolateral Na(+)-H+ exchanger were increased 70% after 48 h of acidification, and there were no changes in transcripts encoding cytoskeletal gamma-actin or glyceraldehyde-3-phosphate dehydrogenase. We conclude that conditions simulating chronic metabolic acidosis coordinately increase the transport activity and transcript levels of the basolateral Na(+)-H+ exchanger in porcine renal epithelial cells.

This article has been cited by other articles:

				R. Oliver III, E. Friday, F. Turturro, A. Lacy, and T. Welbourne Troglitazone's rapid and sustained activation of ERK1/2 induces cellular acidosis in LLC-PK1-F+ cells: physiological responses Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1257 - F1266. [Abstract] [Full Text] [PDF]

				T. Welbourne, E. Friday, R. Fowler, F. Turturro, and I. Nissim Troglitazone acts by PPAR{gamma} and PPAR{gamma}-independent pathways on LLC-PK1-F+ acid-base metabolism Am J Physiol Renal Physiol, January 1, 2004; 286(1): F100 - F110. [Abstract] [Full Text] [PDF]

				H. Hayashi, K. Szaszi, N. Coady-Osberg, J. Orlowski, J. L. Kinsella, and S. Grinstein A Slow pH-dependent Conformational Transition Underlies a Novel Mode of Activation of the Epithelial Na+/H+ Exchanger-3 Isoform J. Biol. Chem., March 22, 2002; 277(13): 11090 - 11096. [Abstract] [Full Text] [PDF]

				A. Garciandia, R. Lopez, J. Tisaire, A. Arrazola, A. Fortuno, J. Bueno, and J. Diez Enhanced Na+-H+ Exchanger Activity and NHE-1 mRNA Expression in Lymphocytes From Patients With Essential Hypertension Hypertension, March 1, 1995; 25(3): 356 - 364. [Abstract] [Full Text]