Kinetics of sodium succinate cotransport across renal brush-border membranes

The kinetics of Na/succinate cotransport across renal brush-borders was studied using membrane vesicles. Initial rates of succinate uptake (Js) were estimated from 1-s uptakes measured under voltage-clamped conditions. Lowering the external (cis) sodium concentration reduced the succinate Kt without affecting the Jsmax. Increasing the intravesicular (trans) sodium concentration reduced both Jsmax and Kt. This trans inhibition by Na was relieved by trans-succinate. Varying the membrane potential from -60 to +60 reduced succinate transport in an exponential manner, which was reflected by a Kt effect, i.e. an increase in the Kt with no change in Jsmax. The membrane potential results suggest that the succinate/sodium-carrier complex bears a net positive charge. On the basis of these and earlier observations, we propose that Na/succinate cotransport across renal brush-borders is described by an Iso Ordered Quad Quad reaction kinetics in which three Na ions first bind to the carrier to increase its affinity for succinate.