Functional differences between rabbit and human Na(+)-dicarboxylate cotransporters, NaDC-1 and hNaDC-1

The rabbit and human Na(+)-dicarboxylate cotransporters, NaDC-1 and hNaDC-1, were expressed in Xenopus oocytes, and the transport of succinate, citrate, and glutarate was compared. Both transporters had similar affinities for succinate and glutarate, with Michaelis-Menten constant (K(m)) values of approximately 0.5- 0.8 mM (succinate) and 6-7 mM (glutarate), verifying that they are low-affinity sodium-dependent dicarboxylate transporters. The two transporters differed in their handling of citrate. At pH 7.5, the K(m) value for citrate was 0.9 mM in the rabbit NaDC-1 and 7 mM in the human hNaDC-1. However, the human transporter was more sensitive to pH than the rabbit. At pH 5.5, the K(m) value for citrate decreased to 1.2 mM in hNaDC-1 and decreased to 0.3 mM in the rabbit transporter. Both transporters had Hill coefficients between 1.6 and 2.1, suggesting that multiple sodium ions are coupled to the transport of divalent anions. However, the human transporter, hNaDC-1, had a lower apparent affinity for sodium (KNa, 78 mM) than the rabbit transporter (KNa, 41 mM). In addition, the human hNaDC-1 was relatively insensitive to inhibition by lithium, furosemide, and flufenamate compared with the rabbit NaDC-1. The differences between the human and rabbit transporters may account for observed differences in renal handling of citrate between species.