The mechanism of Na+-L-lactate cotransport by brush-border membrane vesicles from horse kidney. Analysis by isotopic exchange kinetics of a sequential model and stoichiometry.

The present study determines the characteristics of isotopic Na and lactate exchange under equilibrium conditions in horse kidney brush-border membrane vesicles. The influence of one solute (Na+ or lactate) on the isotopic exchange of the co-transported species (lactate or Na) was analyzed in detail. Analysis of the data suggests that Na and lactate interact sequentially with the carrier. The observed apparent symmetry between the activating effect of low Na concentrations and the inhibiting effect of high Na concentrations on the lactate exchange process suggests that the carrier functions according to a glide symmetry model where the two solutes bind to the carrier according to an iso-ordered Bi Bi process. This conclusion is strengthened by the properties of the 22Na exchange process catalyzed by the lactate carrier. Direct measurement under equilibrium conditions of the coupled Na+/lactate transport indicated a stoichiometry of 2:1. These data, along with those obtained in a previous study (Mengual R., and Sudaka P. (1983) J. Membr. Biol. 71, 163-171) allow us to propose a mechanism for the Na+-lactate cotransport, involving a transport system that functions according to an iso-ordered Bi Bi process where binding and debinding of Na+ occur first, followed by the lactate molecule.