Am J Physiol Cell Physiol AJP: Cell Physiology
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Am J Physiol Cell Physiol (April 7, 2004). doi:10.1152/ajpcell.00582.2003
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Submitted on December 30, 2003
Accepted on March 18, 2004

Extracellular Na+ inhibits Na+ /H+ exchange -Cell shrinkage reduces the inhibition

Philip B Dunham1*, Scott J Kelley1, and Paul J Logue1

1 Biology, Syracuse University, Syracuse, NY, USA

* To whom correspondence should be addressed. E-mail: pbdunham{at}syr.edu.

Na+/H+ exchangers, NHE, are ubiquitous transporters participating in regulation of cell volume and pH. Cell shrinkage, acidification, and growth factors activate NHE by increasing its sensitivity to intracellular H+ concentration. In this study, the kinetics were studied in dog red blood cells of Na+ influx through NHE as a function of external Na+ concentration, Nao. In cells in isotonic media, external Na+ inhibited Na+ influx above 40 mM. Osmotic shrinkage activated NHE by reducing this inhibition. In cells in hypertonic media (isotonic media + 120 mM sucrose), there was no inhibition and influx was a hyperbolic function of Nao. The kinetics of Na+-inhibited Na+ influx were analyzed at various extents of osmotic shrinkage. The curves for inhibited Na+ fluxes were sigmoid, indicating more than one Na+ inhibitory site associated with each transporter. Shrinkage increased significantly the K1/2 of Na+-inhibited Na+ influx, the mechanism by which shrinkage activates NHE.




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