Sodium–hydrogen antiporter

The sodium–hydrogen antiporter or sodium–proton exchanger (Na+/H+ exchanger or NHX) is a membrane protein that transports Na⁺ into the cell, and H⁺ out of the cell (antiport).

Na+/H+ antiporter 1
Identifiers
Symbol	Na_H_antiport_1
Pfam	PF06965
InterPro	IPR004670
TCDB	2.A.36
OPM superfamily	106
OPM protein	1zcd
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Function

They are found in the membranes of many cells, and especially in those of the nephron of the kidney, specifically in the intercalary cells of the collecting duct and in the epithelial cells of the proximal convoluted tubule. The membrane pump is primarily responsible for maintaining homeostasis of pH and sodium.^[1] Defects in Na+/H+ antiporters may result in heart or kidney failure.^[2] Angiotensin II upregulates this antiporter in the proximal convoluted tubule in order to promote Na⁺ reabsorption and H⁺ secretion. Na+/H+ exchangers are thought to be implicated in other disorders such as hypertension. In one study, transgenic mice over expressing this membrane protein were shown to have increased reabsorption and retention of sodium after increased salt intake.^[3]

In dopamine receptor signalling,^[4] the widely expressed Na+/H+ exchanger NHE-1 is activated downstream of the D2,^[5] D3,^[6][7] and D4 receptors.^[8]

Isoforms

There are several isoforms of the antiporter:

• Sodium–hydrogen antiporter 1
• Sodium–hydrogen antiporter 2
• Sodium–hydrogen antiporter 3
• Sodium–hydrogen antiporter 4
• Sodium–hydrogen antiporter 5
• Sodium–hydrogen antiporter 6
• Sodium–hydrogen antiporter 7
• Sodium–hydrogen antiporter 8
• Sodium–hydrogen antiporter 9

Families

There are several families of sodium/proton antiporters that facilitate the exchange of sodium ions with protons across the lipid membrane. Some of them include:^[9]

• TC# 2.A.33 - Na⁺:H⁺ Antiporter (NhaA) Family
• TC# 2.A.34 - Na⁺:H⁺ Antiporter (NhaB) Family
• TC# 2.A.35 - Na⁺:H⁺ Antiporter (NhaC) Family
• TC# 2.A.36 - Monovalent Cation:Proton Antiporter-1 (CPA1) Family
• TC# 2.A.37 - Monovalent Cation:Proton Antiporter-2 (CPA2) Family
• TC# 2.A.62 - Na⁺:H⁺ Antiporter (NhaD) Family
• TC# 2.A.63 - Monovalent Cation (K⁺ or Na⁺):Proton Antiporter-3 (CPA3) Family
• TC# 2.A.111 - Na⁺:H⁺ Antiporter (NhaE) Family

References

1. Padan E, Landau M (2016). "Chapter 12: Sodium-Proton (Na⁺/H⁺) Antiporters:Properties and Roles in Health and Disease". In Sigel A, Sigel H, Sigel RK (eds.). The Alkali Metal Ions: Their Role in Life. Metal Ions in Life Sciences. Vol. 16. Springer. pp. 391–458. doi:10.1007/978-3-319-21756-7_12. ISBN 978-3-319-21755-0. PMID 26860308.
2. Bobulescu IA, Moe OW (September 2006). "Na+/H+ exchangers in renal regulation of acid-base balance". Seminars in Nephrology. 26 (5): 334–44. doi:10.1016/j.semnephrol.2006.07.001. PMC 2878276. PMID 17071327.
3. Kuro-o, M (January 1995). "Salt-sensitive hypertension in transgenic mice overexpressing Na(+)-proton exchanger". Circulation Research. 76 (1): 148–153. doi:10.1161/01.res.76.1.148. PMID 8001273.
4. Yun CH, Tse CM, Nath SK, Levine SA, Brant SR, Donowitz M (July 1995). "Mammalian Na+/H+ exchanger gene family: structure and function studies". The American Journal of Physiology. 269 (1 Pt 1): G1–11. doi:10.1152/ajpgi.1995.269.1.G1. PMID 7631785.
5. Neve KA, Kozlowski MR, Rosser MP (December 1992). "Dopamine D2 receptor stimulation of Na+/H+ exchange assessed by quantification of extracellular acidification". The Journal of Biological Chemistry. 267 (36): 25748–53. PMID 1361188.
6. Cox BA, Rosser MP, Kozlowski MR, Duwe KM, Neve RL, Neve KA (September 1995). "Regulation and functional characterization of a rat recombinant dopamine D3 receptor". Synapse. 21 (1): 1–9. doi:10.1002/syn.890210102. PMID 8525456.
7. Chio CL, Lajiness ME, Huff RM (January 1994). "Activation of heterologously expressed D3 dopamine receptors: comparison with D2 dopamine receptors". Molecular Pharmacology. 45 (1): 51–60. PMID 8302280.
8. Chio CL, Drong RF, Riley DT, Gill GS, Slightom JL, Huff RM (April 1994). "D4 dopamine receptor-mediated signaling events determined in transfected Chinese hamster ovary cells". The Journal of Biological Chemistry. 269 (16): 11813–9. PMID 7512953.
9. "TCDB » HOME". Transporter Classification Database. Retrieved 2016-03-14.

External links

• Sodium-Hydrogen+Exchanger at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the public domain Pfam and InterPro: IPR004670