The human Na+ glucose cotransporter is a molecular water pump.

Abstract

The human small intestine absorbs approximately 9 L of water per day, thus establishing this organ as an important contributor to whole‐body water homeostasis. However, the mechanism by which water transport occurs in the small intestine has been an issue of debate for nearly 40 years. To examine the involvement of the human sodium‐glucose transporter (hSGLT1) in water transport across the brush border membrane, hSGLT1 was expressed in Xenopus larvis. 1 These test oocytes were shown to express > 1011 copies of hSGLT1 per cell, and transport activity was quantified with high precision by measuring the inward sodium current stimulated by the addition of α‐methyl‐glucose, a glucose analog that is transported by hSGLT1 but is not metabolized within the enterocyte. Sensitive optical techniques allowed for simultaneous measurement of oocyte volume during hSGLT1 transport. The addition of α‐methyl‐glucose to the media bathing test oocytes results in an immediate increase in hSGLT1 transport and an abrupt swelling of the oocyte. The hSGLT1 transport of two sodium ions and one α‐methyl‐glucose molecule was coupled, within the protein itself, to the influx of 210 water molecules. This stoichiometric relationship between sodium, sugar, and water during hSGLT1 transport was constant and independent of external parameters such as sodium concentrations, sugar concentrations, transmembrane voltages, temperature, and osmotic gradients. In control experiments with oocytes expressing ion channels or oocytes doped with ionophores, only delayed water flow occurred due to increased internal osmolarity.1 This observation demonstrates that the rapid coupling of water transport to sodium and glucose transport occurs within the hSGLT1 protein, rather than as a rapid response to the osmotic gradients generated indirectly by activity of this protein. In summary, hSGLT1 functions not only as a sodium and sugar transporter but also as a molecular water pump. These data suggest that hSGLT1 may account for almost half of the daily water uptake in the small intestine.1