Kinetics of the Reverse Mode of the Na+/Glucose Cotransporter

Kinetics of the Reverse Mode of the Na+/Glucose Cotransporter

Model Status

This CellML model is in the process of being curated, the units are consistent and the model runs in COR and PCEnv. This model does not yet recreate all the published results.

Model Structure

Abstract: This study investigates the reverse mode of the Na/glucose cotransporter (SGLT1). In giant excised inside-out membrane patches from Xenopus laevis oocytes expressing rabbit SGLT1, application of a-methyl-D-glucopyranoside (aMDG) to the cytoplasmic solution induced an outward current from cytosolic to external membrane surface. The outward current was Na- and sugar-dependent, and was blocked by phlorizin, a specific inhibitor of SGLT1. The current-voltage relationship saturated at positive membrane voltages (30-50 mV), and approached zero at -150 mV. The half-maximal concentration for aMDG-evoked outward current (K_0.5_aMDG) was 35 mM (at 0 mV). In comparison, K_0.5_aMDG for forward sugar transport was 0.15 mM (at 0 mV). K_0.5_Na was similar for forward and reverse transport (~ 35mM at 0 mV). Specificity of SGLT1 for reverse transport was: aMDG (1.0) > D-galactose (0.84) > 3-O-methyl-glucose (0.55) > D-glucose (0.38), whereas for forward transport, specificity was: aMDG ~ D-glucose ~ D-galactose > 3-O-methylglucose. Thus there is an asymmetry in sugar kinetics and specificity between forward and reverse modes. Computer simulations showed that a 6-state kinetic model for SGLT1 can account for Na/sugar cotransport and its voltage dependence in both the forward and reverse modes at saturating sodium concentrations. Our data indicate that under physiological conditions, the transporter is poised to accumulate sugar efficiently in the enterocyte.

The original paper reference is cited below:

Kinetics of the Reverse Mode of the Na+/Glucose Cotransporter, S.Eskandari, E.M. Wright and D.D.F. Loo, 2005, Journal of Membrane Biology, 204, 23-32. PubMed ID: 16007500

Schematic diagram of the Eskandari et al 2005 SGLT1 model. C' represents the external-facing carrier. C'' represents the internal-facing carrier.