Na+/H+ Exchanger

Sodium-hydrogen exchangers (Na+/H+ exchangers, NHE) are ATP-independent membrane glycoprotein transporters that are involved in the regulation of intracellular pH, cell volume and the cellular response to hormones and mitogens.

Products
Background
Literature
Gene Data

Inhibitors

Cat No Product Name / Activity
0890 Amiloride hydrochloride
Na+ channel blocker; inhibits NHE1
5512 BIX NHE1 inhibitor
Potent and selective NHE1 inhibitor
5358 Cariporide
Selective NHE1 inhibitor; cardioprotective and antitumor
3378 EIPA
Inhibits TRPP3-mediated currents; also inhibits the Na+/H+ exchanger (NHE)
2727 Zoniporide dihydrochloride
Selective NHE1 inhibitor

Sodium-hydrogen exchangers (Na+/H+ exchangers, NHE) are ATP-independent membrane glycoprotein transporters that are involved in the regulation of intracellular pH, cell volume and the cellular response to hormones and mitogens. The transporters mediate the simultaneous efflux of a hydrogen ion and the influx of a sodium ion across the plasma membrane, the driving force being the inwardly directed electrochemical Na+ gradient. There are nine known mammalian NHE isoforms (NHE1-9), all of which differ in specific biological function as well as subcellular localization.

NHE1, the most well characterized NHE isoform, mediates transepithelial transport in secretory parotid acinar cells and may also mediate ammonium reabsorption in the kidney. NHE2 is also expressed in the parotid gland, where it regulates Na+ secretion in addition to its involvement in NaHCO3 absorption in the kidney. Unlike the other NHE isoforms, NHE3 is recycled between apical membranes and the endosomal compartment of epithelial cells where it has a significant involvement in renal and intestinal Na+ absorption. Aside from their roles in regulating intracellular pH and volume, little is known about further functions of NHE4, NHE5, NHE6, NHE7, NHE8 and NHE9.

In addition to their integral involvement in the control of intracellular pH and volume, the NHE family has also been implicated in diseases including hypertension and organ ischemia. Transgenic NHE1 overexpression results in salt-sensitive hypertension in rodents, whilst NHE1 activity in peripheral blood mononuclear cells (PBMCs) from hypertensive patients is directly correlated with increased blood pressure. Whilst the exact mechanism by which NHE activity influences blood pressure remains unknown, it has been suggested to involve the reversal of the Na+/Ca2+ exchanger (NCX); this leads to increased intracellular Ca2+ concentration, driving vascular smooth muscle cell contraction.

The involvement of NHE activity during organ ischemia is complex: H+ efflux driven by the NHE corrects the drop in intracellular pH, yet the concurrent influx of Na+ ions leads to Ca2+ overload through the actions of the NCX. Increased intracellular calcium leads to tissue damage through mechanisms of cellular necrosis and apoptosis that include the opening of the mitochondrial permeability transition pore (MPTP). This paradox, known as the pH paradox, is the driving mechanism behind reperfusion injury following cardiac, renal or cerebral ischemia. In support of the integral involvement of NHE activity during organ ischemia, NHE1 inhibition has been shown to exert a protective effect during cardiac ischemia.

Literature for Na+/H+ Exchanger

Cardiovascular

Cardiovascular Research Product Guide

A collection of over 250 products for cardiovascular research, the guide includes research tools for the study of:

  • Hypertension
  • Thrombosis and Hemostasis
  • Atherosclerosis
  • Myocardial Infarction
  • Ischemia/Reperfusion Injury
  • Arrhythmias
  • Heart Failure

Na+/H+ Exchanger Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
Solute carrier family 9, subfamily A member 1 (NHE1) Human SLC9A1 NM_003047 P19634
Mouse Slc9a1 NM_016981 Q61165
Rat Slc9a1 NM_012652 P26431
Solute carrier family 9, subfamily A member 2 (NHE2) Human SLC9A2 NM_003048 Q9UBY0
Mouse Slc9a2 NM_001033289 Q3ZAS0
Rat Slc9a2 NM_012653 P48763
Solute carrier family 9, subfamily A member 3 (NHE3) Human SLC9A3 NM_004174 P48764
Mouse Slc9a3 NM_001081060 G3X939
Rat Slc9a3 NM_012654 P26433
Solute carrier family 9, subfamily A member 4 (NHE4) Human SLC9A4 NM_001011552.3 Q6AI14
Mouse Slc9a4 NM_177084 Q8BUE1
Rat Slc9a4 NM_173098 P26434
Solute carrier family 9, subfamily A member 5 (NHE5) Human SLC9A5 NM_004594 Q14940
Mouse Slc9a5 NM_001081332 B2RXE2
Rat Slc9a5 NM_138858 Q9Z0X2
Solute carrier family 9, subfamily A member 6 (NHE6) Human SLC9A6 NM_006359 Q92581
Mouse Slc9a6 NM_172780 A1L3P4
Rat Slc9a6 XM_001053956 D3ZWQ4
Solute carrier family 9, subfamily A member 7 (NHE7) Human SLC9A7 NM_032591 Q96T83
Mouse Slc9a7 NM_177353 Q8BLV3
Rat - - -
Solute carrier family 9, subfamily A member 8 (NHE8) Human SLC9A8 XM_030524 Q9Y2E8
Mouse Slc9a8 NM_148929 Q8R4D1
Rat Slc9a8 NM_001025281 Q4L208
Solute carrier family 9, subfamily A member 9 (NHE9) Human SLC9A9 NM_173653 Q8IVB4
Mouse Slc9a9 NM_177909 Q8BZ00
Rat Slc9a9 XM_001064905 -