Isotonic transport by the Na+-glucose cotransporter SGLT1 from humans and rabbit

1. In order to study its role in steady state water transport, the Na+-gluc ose cotransporter (SGLT1) nas expressed in Xenopus laevis oocytes; both the human and the rabbit clones were tested. The transport activity was monito red as a clamp current and the flux of water followed optically as the chan ge on oocyte volume 2. SGLT1 has two modes of water transport. First, it acts as a molecular wa ter pump: for each 2 Na+ and 1 sugar molecule 264 water molecules were cotr ansported in the human SGLT1 (hSGLT1), 424 for the rabbit SGLT1 (rSGLT1). S econd, it acts as a water channel. 3. The cotransport of water was tightly coupled to the sugar-induced clamp current. Instantaneous changes in clamp current induced by changes in clamp voltage were accompanied by instantaneous changes in the rate of water tra nsport. 4. The cotransported solution was predicted to be hypertonic, and an osmoti c gradient built up across the oocyte membrane with continued transport; th is resulted in an additional osmotic influx of water. After 5-10 min a stea dy state was achieved in which the total influx was predicted to be isotoni c with the intracellular solution. 5. With the given expression levels, the steady state water transport was d ivided about equally between cotransport, osmosis across the SGLT1 and osmo sis across the native oocyte membrane. 6. Coexpression of AQP1 with the SGLT1 increased the water permeability mor e than 10-fold and steady state isotonic transport was achieved after less than 2 s of sugar activation. One-third of the water was cotransported, and the remainder was osmotically driven through the AQP1. 7. The data, suggest that SGLT1 has three roles: in isotonic water transpor t: it cotransports water directly, it supplies a passive pathway for osmoti c water transport, and it generates an osmotic driving force that can be em ployed by other pathways, for example aquaporins.