FUNCTIONAL DIFFERENCES BETWEEN RABBIT AND HUMAN NA-DICARBOXYLATE COTRANSPORTERS, NADC-1 AND HNADC-1()

The rabbit and human Na+-dicarboxylate cotransporters, NaDC-1 and hNaD C-1, were expressed in Xenopus oocytes, and the transport of succinate , citrate, and glutarate was compared. Both transporters had similar a ffinities for succinate and glutarate, with Michaelis-Menten constant (K-m) values of similar to 0.5-0.8 mM (succinate) and 6-7 mM (glutarat e), verifying that they are low-affinity sodium-dependent dicarboxylat e transporters. The two transporters differed in their handling of cit rate. At pH 7.5, the K-m value for citrate was 0.9 mM in the rabbit Na DC-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 ci trate decreased to 1.2 mM in hNaDC-1 and decreased to 0.3 mM in the ra bbit transporter. Both transporters had Hill coefficients between 1.6 and 2.1, suggesting that multiple sodium ions are coupled to the trans port of divalent anions. However, the human transporter, hNaDC-1, had a lower apparent affinity for sodium (K-Na, 78 mM) than the rabbit tra nsporter (K-Na, 41 mM). In addition, the human hNaDC-1 was relatively insensitive to inhibition by lithium, furosemide, and flufenamate comp ared with the rabbit NaDC-1. The differences between the human and rab bit transporters may account for observed differences in renal handlin g of citrate between species.