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Am J Physiol Cell Physiol 289: C1159-C1168, 2005. First published June 8, 2005; doi:10.1152/ajpcell.00295.2004
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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Functional characterization of high-affinity Na+/dicarboxylate cotransporter found in Xenopus laevis kidney and heart

Naomi Oshiro and Ana M. Pajor

Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas

Submitted 23 June 2004 ; accepted in final form 5 June 2005

The SLC13 gene family includes sodium-coupled transporters for citric acid cycle intermediates and sulfate. The present study describes the sequence and functional characterization of a SLC13 family member from Xenopus laevis, the high-affinity Na+/dicarboxylate cotransporter xNaDC-3. The cDNA sequence of xNaDC-3 codes for a protein of 602 amino acids that is ~70% identical to the sequences of mammalian NaDC-3 orthologs. The message for xNaDC-3 is found in the kidney, liver, intestine, and heart. The xNaDC-3 has a high affinity for substrate, including a Km for succinate of 4 µM, and it is inhibited by the NaDC-3 test substrates 2,3-dimethylsuccinate and adipate. The transport of succinate by xNaDC-3 is dependent on sodium, with sigmoidal activation kinetics, and lithium can partially substitute for sodium. As with other members of the family, xNaDC-3 is electrogenic and exhibits inward substrate-dependent currents in the presence of sodium. However, other electrophysiological properties of xNaDC-3 are unique and involve large leak currents, possibly mediated by anions, that are activated by binding of sodium or lithium to a single site.

SLC13 gene family; citric acid cycle intermediate; lithium



Address for reprint requests and other correspondence: A. M. Pajor, Dept. of Human Biological Chemistry and Genetics, Univ. of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0645 (e-mail: ampajor{at}utmb.edu)




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A. M. Pajor and K. M. Randolph
Inhibition of the Na+/Dicarboxylate Cotransporter by Anthranilic Acid Derivatives
Mol. Pharmacol., November 1, 2007; 72(5): 1330 - 1336.
[Abstract] [Full Text] [PDF]




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