The small-intestinal Na+, D-glucose cotransporter: an asymmetric gated channel (or pore) responsive to delta psi

At delta psi approximately equal to 0, D-glucose influx into, and efflux out of, membrane vesicles from small-intestinal brush borders are affected by trans Na+ and trans D-glucose to different extents. D-glucose influx and efflux respond to delta psi (negative at the trans side) to different extents. The small-intestinal Na+, D-glucose cotransporter is thus functionally asymmetric. This is not unexpected, in view of the structural asymmetry previously found. The characteristics of the delta psi-dependence of transinhibition by D-glucose are compatible with the mobile part of the cotransporter bearing a negative charge of at least 1 (in the substrate-free form). They are not compatible with its mobile part being electrically neutral. Pertinent equations are given in the Appendix. Partial Cleland's kinetic analysis and other criteria rule out (Iso) Ping Pong mechanisms and makes likely a Preferred Ordered mechanism, with Na+out binding to the cotransporter prior to the sugarout. A likely model is proposed aimed at providing a mechanism of flux coupling and active accumulation.