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The Human Na+ Glucose Cotransporter Is a Molecular Water Pump

University of Illinois at Urbana-Champaign

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 -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 -methyl-glucose to the media bathing test oocytes results in an immediate increase in hSGLT ₁ transport and an abrupt swelling of the oocyte. The hSGLT₁ transport of two sodium ions and one -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 hSGLT ₁ protein, rather than as a rapid response to the osmotic gradients generated indirectly by activity of this protein. In summary, hSGLT ₁ 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

Journal of Parenteral and Enteral Nutrition, Vol. 23, No. 3, 173-174 (1999)
DOI: 10.1177/0148607199023003173


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