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Am J Physiol Cell Physiol 287: C64-C72, 2004. First published February 18, 2004; doi:10.1152/ajpcell.00061.2003
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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

OKP cells express the Na-dicarboxylate cotransporter NaDC-1

Seiji Aruga,1 Ana M. Pajor,3 Kiyoshi Nakamura,1 Liping Liu,1 Orson W. Moe,1,2 Patricia A. Preisig,1 and Robert J. Alpern1

1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75390; 2Veterans Administration Medical Center, Dallas 75216; and 3Department of Physiology, University of Texas Medical Branch, Galveston, Texas 77555

Submitted 12 February 2003 ; accepted in final form 11 February 2004

Urinary citrate concentration, a major factor in the formation of kidney stones, is primarily determined by its rate of reabsorption in the proximal tubule. Citrate reabsorption is mediated by the Na-dicarboxylate cotransporter-1 (NaDC-1). The opossum kidney (OKP) cell line possesses many characteristics of the renal proximal tubule. The OKP NaDC-1 (oNaDC-1) cDNA was cloned and encodes a 2.4-kb mRNA. When injected into Xenopus oocytes, the cotransporter is expressed and demonstrates Na-coupled citrate transport with a stoichiometry of ≥3 Na:1 citrate, specificity for di- and tricarboxylates, pH-dependent citrate transport, and pH-independent succinate transport, all characteristics of the other NaDC-1 orthologs. Chronic metabolic acidosis increases proximal tubule citrate reabsorption, leading to profound hypocitraturia and an increased risk for stone formation. Under the conditions studied, endogenous OKP NaDC-1 mRNA abundance is not regulated by changes in media pH. In OKP cells transfected with a green fluorescent protein-oNaDC-1 construct, however, media acidification increases Na-dependent citrate uptake, demonstrating posttranscriptional acid regulation of NaDC-1 activity.

citrate; acid base; nephrocalcinosis; nephrolithiasis; opossum kidney cells


Address for reprint requests and other correspondence: P. A. Preisig, Dept. of Internal Medicine, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Rm. H5.112, Dallas, TX 75390-8856 (E-mail: patricia.preisig{at}utsouthwestern.edu).




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[Abstract] [Full Text] [PDF]


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