Sodium–hydrogen antiporter explained

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).

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

Notes and References

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