Chapter 20 The Mechanism of Coupling between Glucose Transport and Electrical Potential in the Proximal Tubule: A Study of Potential-Dependent Phlorizin Binding to Isolated Renal Microvillus Membranes

Abstract

Publisher Summary This chapter describes the mechanism of high-affinity phlorizin binding to isolated renal microvillus membrane vesicles as a function of imposed alterations in the transmembrane electrical potential difference. The glucose transport across the luminal membrane of the proximal tubular cell occurs via cotransport with Na + , and such a cotransport mechanism allows the energization of uphill glucose transport by the electrochemical Na + gradient; in particular, glucose uptake into isolated brush border membrane vesicles may be stimulated by imposing an inside-negative electrical potential difference across the membrane. Phlorizin—a competitive inhibitor of brush border glucose transport—binds to an Na + -dependent, high-affinity receptor on the microvillus membrane that is thought to be identical with the Na + -coupled glucose carrier; however, phlorizin is not itself transported across the brush border membrane by the Na + -coupled sugar transport system. The data presented in the chapter are more consistent with an effect of potential on the initial interaction of sugar with the binding site prior to translocation. However, the experiments described in the chapter cannot distinguish an effect of potential to modulate the appearance of a negatively charged carrier at the membrane surface from an effect to modify carrier activation with respect to substrate binding. This suggests that the coupling between glucose transport and the transmembrane electrical potential difference arises from potential-dependent behavior of the free carrier rather than from potential dependence of the sugar translocation step per se.