Multiple modes of regulation of Na+/H+ exchangers

Ann N Y Acad Sci. 2002 Nov:976:248-58. doi: 10.1111/j.1749-6632.2002.tb04747.x.


Mammalian Na(+)/H(+) exchangers (NHE) mediate electroneutral countertransport of H(+) for Na(+) across the plasmalemmal and organellar membranes. They contribute to cellular and organellar pH and volume regulation and transepithelial Na(+) transport. The aim of this review is to illustrate the complex regulation of these transporters by focusing on the multiple mechanisms controlling the epithelial isoform, NHE3. A variety of agents and conditions (e.g., hormones, growth factors, cellular pH, and medium osmolarity) act in concert to achieve short-term and long-term regulation of this isoform. The underlying mechanism involves changes in the number of transporters on the cell surface and/or altered activity of the individual exchangers due to allosteric activation by intracellular protons, phosphorylation and interaction with accessory proteins and the cytoskeleton. A similar regulatory versatility probably applies to other NHE isoforms, and the lessons learned from studying members of the NHE family could serve as a useful reference when exploring the modes and levels of regulation of other transporters.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Cell Membrane / metabolism
  • Electrophysiology
  • Hormones / physiology
  • Hydrogen-Ion Concentration
  • Intracellular Membranes / metabolism
  • Phosphorylation
  • Protons
  • Sodium / metabolism
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers / genetics
  • Sodium-Hydrogen Exchangers / physiology*


  • Hormones
  • Protons
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers
  • Sodium