SODIUM-GLUCOSE COTRANSPORTERS DISPLAY SODIUM-DEPENDENT AND PHLORHIZIN-DEPENDENT WATER PERMEABILITY

Expression of Na+-glucose cotransporters of the SGLT-1 type by Xenopus laevis oocytes increased the osmotic water permeability (P-f) of oocy tes by a factor of 1.9-2.8, in the presence and in the absence of 5 mM extracellular glucose. The P-f increase was correlated with the amoun t of SGLT-1 cRNA injected. In oocytes expressing SGLT-1, either additi on of phlorizin to the medium or the replacement of Na+ by choline inh ibited the uptake of methyl-alpha-D-glucopyranoside, a specific substr ate for SGLT-1, and returned oocyte P-f to its level in uninjected ooc ytes. Phlorizin inhibited the SGLT-1-attributable increase in P-f with an inhibition constant (K-i) of 6.1 mu M, a value analogous to the K- i for phlorizin inhibition of sugar uptake. However, neither the prese nce of phlorizin nor the absence of extracellular Na+ significantly af fected the increase in P-f elicited in oocytes expressing GLUT-1, a fa cilitative glucose transporter. These findings suggest that SGLT-1 for ms a pore that allows the transmembrane passage of water and that wate r and glucose traverse the protein through this pore. The finding that removal of extracellular Na+ abolishes the increase in P-f attributab le to SGLT-1 suggests that extracellular Na+ is required to maintain p atency of this transporter's water-permeable transmembrane pore.