The transport properties of the human renal Na+- dicarboxylate cotransporter under voltage-clamp conditions

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Abstract
The transport properties of the human Na+-dicarboxylate cotransporter, (hNaDC-1), expressed in Xenopus laevis oocytes were characterized using the two-electrode voltage clamp technique. Steady-state succinate-evoked inward currents in hNaDC-1 were dependent on the concentrations of succinate and sodium, and on the membrane potential. At −50 mV, the half-saturation constant for succinate ( K0.5succinate) was 1.1 mM and the half-saturation constant for sodium ( K0.5sodium) was 65 mM. The Hill coefficient was 2.3, which is consistent with a transport stoichiometry of 3 Na+:1 divalent anion substrate. The hNaDC-1 exhibits a high-cation selectivity. Sodium is the preferred cation and other cations, such as lithium, were not able to support transport of succinate. The preferred substrates of hNaDC-1 are fumarate ( K0.51.8 mM) and succinate, followed by methylsuccinate ( K0.52.8 mM), citrate ( K0.56.8 mM) and α-ketoglutarate ( K0.516 mM). The hNaDC-1 may also transport sodium ions through an uncoupled leak pathway, which is sensitive to phloretin inhibition. We propose a transport model for hNaDC-1 in which the binding of three sodium ions is followed by substrate binding.