Secondary active glucose transport occurs by at least four members of the SLC5 gene family. This review considers the structure and function of two premier members, SGLT1 and SGLT2, and their role in intestinal glucose absorption and renal glucose reabsorption. Genetics disorders of SGLTs include GlucoseGalactose Malabsorption, and Familial Renal Glucosuria. SGLT1 plays a central role in Oral Rehydration Therapy used so effectively to treat secretory diarrhoea such as cholera. Increasing attention is being focused on SGLTs as drug targets for the therapy of diabetes.
In addition to the Na+‐coupled GABA transport, the Na+/Cl− dependent GABA transporter, GAT‐1, also has a Li+‐induced leak. Recently, the amino acids directly involved in the interaction with the Na+ and Li+ ions have been identified (Zhou et al, 2006, JBC Vol. 281). In the present study, we obtain insight into the structural dynamics of the two transport modes of GAT‐1 by applying the voltage clamp fluorometry method (VCF) to wild type GAT‐1 expressed in Xenopus oocytes. We have taken advantage of the only accessible cysteine in wild type rat GAT‐1, C74, and labeled this residue with a cysteine‐reactive fluorophor, tetramethyl rhodamine‐6‐maleinamide.Our fluorescent read‐outs show that the transporter undergoes different voltage dependent conformational changes in the presence of the different ions in the external solution: in Na+ buffer the V½ for fluorescence is −2 ± 9 mV whereas in Li+ buffer it is −71 ± 12 mV. The time courses of these fluorescent changes are also highly dependent on the cation: in Na+ the τmax is 120 ms and in Li+ it is 40 ms. The fluorescence data for Li+ correlates with the Li+ induced currents: these are highly voltage dependent and only present at hyperpolarized potentials (<−50 mV).The study demonstrates the advantage of applying the VCF method in combination with homology modeling of the neurotransmitter transporters to the newly crystallized bacterial homolog, LeuT.
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