Background/Aims: Slc26a7 is a member of a family of anion transport proteins, Solute-Linked Carrier 26 (Slc26). Slc26a7, which can mediate Cl–/HCO3– exchange, is expressed in the acid-secreting, A-intercalated cells of the kidney collecting duct. On the basolateral side of the A-intercalated cells, Slc26a7 co-localizes with the anion exchanger 1 (AE1), a Cl–/HCO3– exchanger that mediates bicarbonate reabsorption in the collecting duct. Methods: To test if Slc26a7 is involved in acid-base regulation, as its localization and function suggest, we examined the effect of acid loading and deletion of AE1 on Slc26a7 expression with quantitative real-time RT-PCR and Western blotting. Results: Four days of acid loading increased Slc26a7 mRNA expression in the kidney inner medulla by 57% (n = 6 acid loaded vs. n = 6 control rats; p < 0.001), whereas mRNA expression in the outer medulla and the cortex did not change. Western blotting analysis demonstrated increased Slc26a7 protein expression in both outer (140%) and inner medulla (50%) in acid-loaded animals (n = 3) compared to controls (n = 3; p < 0.05). The expression of Slc26a7 mRNA was increased by 66% in the kidneys of AE1 knockout mice (n = 5) compared to the wild types (n = 5, p < 0.001). The increase in Slc26a7 mRNA correlated with a twofold increase in protein expression (p < 0.05). Conclusion: We suggest that the increase in Slc26a7 expression caused by acid challenge and deletion of AE1 represents an adaptive response, indicating that Slc26a7 contributes to the regulation of acid-base balance by the kidney.

Keywords:
Acid-base balance, Acidosis, Anion exchange, Bicarbonate transport, Chloride transport
1.
Schuster VL: Function and regulation of collecting duct intercalated cells. Annu Rev Physiol 1993;55:267–288.
2.
Alper SL: Molecular physiology of SLC4 anion exchangers. Exp Physiol 2006;91:153–161.
3.
Petrovic S, Barone S, Xu J, Conforti L, Ma L, Kujala M, Kere J, Soleimani M: SLC26A7: a basolateral Cl–/HCO3– exchanger specific to intercalated cells of the outer medullary collecting duct. Am J Physiol Renal Physiol 2004;286:F161–F169.
4.
Barone S, Amlal H, Xu J, Kujala M, Kere J, Petrovic S, Soleimani M: Differential regulation of basolateral Cl–/HCO3– exchangers SLC26A7 and AE1 in kidney outer medullary collecting duct. J Am Soc Nephrol 2004;15:2002–2011.
5.
Kujala M, Tienari J, Lohi H, Elomaa O, Sariola H, Lehtonen E, Kere J: SLC26A6 and SLC26A7 anion exchangers have a distinct distribution in human kidney. Nephron Exp Nephrol 2005;101:e50–e58.
6.
Dudas PL, Mentone S, Greineder CF, Biemesderfer D, Aronson PS: Immunolocalization of anion transporter Slc26a7 in mouse kidney. Am J Physiol Renal Physiol 2006;290:F937–F945.
7.
Petrovic S, Xu J, Barone S, Seidler U, Alper SL, Lohi H, Kere J, Soleimani M: Identification of a basolateral Cl–/HCO3– exchanger specific to gastric parietal cells. Am J Physiol Gastrointest Liver Physiol 2003;284:G1093–G1103.
8.
Soleimani M, Xu J: SLC26 chloride/base exchangers in the kidney in health and disease. Semin Nephrol 2006;26:375–385.
9.
Petrovic S, Wang Z, Ma L, Soleimani M: Regulation of the apical Cl–/HCO3– exchanger pendrin in rat cortical collecting duct in metabolic acidosis. Am J Physiol Renal Physiol 2003;284:F103–F112.
10.
Peters LL, Shivdasani RA, Liu SC, Hanspal M, John KM, Gonzalez JM, Brugnara C, Gwynn B, Mohandas N, Alper SL, Orkin SH, Lux SE: Anion exchanger 1 (band 3) is required to prevent erythrocyte membrane surface loss but not to form the membrane skeleton. Cell 1996;86:917–927.
11.
Petrovic S, Amlal H, Sun X, Karet F, Barone S, Soleimani M: Vasopressin induces expression of the Cl–/HCO3– exchanger SLC26A7 in kidney medullary collecting ducts of Brattleboro rats. Am J Physiol Renal Physiol 2006;290:F1194–F1201.
12.
Barone S, Amlal H, Kujala M, Xu J, Karet F, Blanchard A, Kere J, Soleimani M: Regulation of the basolateral chloride/base exchangers AE1 and SLC26A7 in the kidney collecting duct in potassium depletion. Nephrol Dial Transplant 2007;22:3462–3470.
13.
Mount DB, Romero MF: The SLC26 gene family of multifunctional anion exchangers. Pflügers Arch 2004;447:710–721.
14.
Kim KH, Shcheynikov N, Wang Y, Muallem S: SLC26A7 is a Cl– channel regulated by intracellular pH. J Biol Chem 2005;280:6463–6470.
15.
Stehberger PA, Shmukler BE, Stuart-Tilley AK, Peters LL, Alper SL, Wagner CA: Distal renal tubular acidosis in mice lacking the AE1 (band3) Cl–/HCO3– exchanger (slc4a1). J Am Soc Nephrol 2007;18:1408–1418.
16.
Karet FE: Inherited distal renal tubular acidosis. J Am Soc Nephrol 2002;13:2178–2184.
17.
Xu J, Nakamura S, Wang Z, Barone S, Soleimani M: Mice deficient in anion transporter Slc26a7 have defective gastric acid secretion and reduced basolateral Cl–/HCO3– exchange activity in outer medullary collecting duct. Renal Week, ASN Annual Meeting 2006, SA-PO016.
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2008
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