Chloride transport and novel insights into salt-sensitive hypertension
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CLINICAL IMPLICATIONS
Chloride transport and novel insights into salt-sensitive hypertension Friedrich C. Luft
Published online: 23 February 2013 # Springer-Verlag Berlin Heidelberg 2013
Solute-linked carrier 26 (SLC26) isoforms are members of a large conserved family of anion exchangers, many of which display highly restricted and distinct tissue distributions. Cloning experiments have identified more than ten SLC26 genes or isoforms (SLC26A1-11) [1]. Transport modes mediated by SLC26 members include the exchange of chloride for bicarbonate, hydroxyl, sulfate, formate, iodide, or oxalate with variable specificity. Several members of SLC26 isoforms are expressed in the kidney, including SLC26A1, SLC26A4 (pendrin), SLC26A6, SLC26A7, and SLC26A11. Each isoform displays a specific nephron segment distribution with a distinct subcellular localization. Current data indicate important roles for the SLC26 family in chloride absorption, vascular volume homeostasis, acid-base regulation, and oxalate excretion in the kidney. Amlal et al. still added another to the list, namely SLC26A9 or Slc26a9 in the mouse [2]. They relied on Slc26a9 “knockout” mice and document that the electrogenic chloride channel/transporter is localized on the apical membrane of principal cells in the renal medullary collecting duct and functions to mediate chloride excretion (Fig. 1). The collecting duct system is the final component of the kidney to influence the body's electrolyte and fluid balance. In humans, the system accounts for 4–5 % of renal sodium and water reabsorption. The principal cells mediate the collecting duct's influence on sodium and potassium balance via sodium channels and
F. C. Luft (*) Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Lindenbergerweg 80, 13125 Berlin, Germany e-mail: [email protected]
potassium channels located on the cell's apical membrane. Aldosterone determines expression of sodium channels with increased aldosterone causing increased expression of luminal sodium channels. Aldosterone increases the number of Na + /K + -ATPase pumps that allow increased sodium reabsorption and potassium secretion. Vasopressin determines the expression of aquaporin channels on the cell surface. Together, aldosterone and vasopressin let the principal cell control the quantity of water that is reabsorbed. Intercalated cells come in α and β varieties and participate in acid-base homeostasis. Amlal et al. found that Slc26a9 gene-deleted mice exhibit reduced chloride excretion when given a high-salt diet (HSD, 7 % salt) or when subjected to water deprivation [2]. The group had earlier reported on SlC26a9 deletion and relevance to gastric surface epithelial cells, where the carrier mediates Cl−/HCO3− exchange [3]. If we are willing to believe tail-cuff blood pressure measurements in mice, Slc26a9 gene-deleted mice have substantially higher blood pressures when given “normal-salt” diet (NSD, 1 % salt) and exhibit a further increa
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