title: Extracellular Na+ inhibits Na+/H+ exchange: cell shrinkage reduces the inhibition.
abstract: 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 ([Na+](o)). In cells in isotonic media, [Na+](o) inhibited Na+ influx >40 mM. Osmotic shrinkage activated NHE by reducing this inhibition. In cells in isotonic media + 120 mM sucrose, there was no inhibition, and influx was a hyperbolic function of [Na+](o). 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 significantly increased the Na+ concentration at half-maximal velocity of Na+-inhibited Na+ influx, the mechanism by which shrinkage activates NHE.
authors.affiliation: Department of Biology, Syracuse University, 130 College Place, Syracuse, NY 13244-1220, USA. pbdunham@syr.edu
authors.forename: Philip B
authors.initials: PB
authors.lastname: Dunham
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Kelley
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Logue
mesh_terms: D000143:Acids / Q000494:pharmacology; D000584:Amiloride / Q000031:analogs & derivatives; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D004232:Diuretics / Q000494:pharmacology; D004285:Dogs; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D007552:Isotonic Solutions / Q000494:pharmacology; D008954:Models, Biological; D009994:Osmolar Concentration; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D012964:Sodium / Q000493:pharmacokinetics*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D013395:Sucrose / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D000143:Acids; D004232:Diuretics; D007552:Isotonic Solutions; D012462:Saline Solution, Hypertonic; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D013395:Sucrose; D000584:Amiloride; D012964:Sodium