In contrast to the central nervous system, EAAT2 expression is mainly limited to satellite glial cells and axons of the sciatic nerve ( Carozzi et al., 2008). These transporters have also been observed in myelinating Schwann cells of the sciatic nerve ( Carozzi et al., 2008).

Dorsal root ganglion (DRG) neurons primarily express EAAT1 and EAAT3 on axons and central terminals ( Carozzi et al., 2008 Tao et al., 2004). Glu transporter levels in the periphery are slightly different from the central nervous system. The most abundant Glu transporter in the lumbar dorsal horn is EAAT2, whereas EAAT3 expression is more prominent in the thoracic and cervical dorsal horns ( Queen et al., 2007). Furthermore, regional specificity is also observed across the spinal cord. EAAT1, EAAT2, and EAAT3 are more prevalent in the dorsal horn than in the ventral horn ( Queen, Kesslak, & Bridges, 2007). Similar cell-type expression profile is seen in the spinal cord as the brain. EAAT5 is expressed explicitly on retinal cells ( Arriza et al., 1997). EAAT3 and EAAT4 are predominantly neuronal with EAAT4 being more prevalent in the cerebellar purkinje neurons ( Fairman et al., 1995). Neurons only express a small portion (~ 6–10%) of EAAT2 at the synapse even though significant reuptake by neurons has previously been shown to occur ( Furness et al., 2008 Suchak et al., 2003). Both of these proteins are mainly found on astrocyte soma and processes with minimal expression in oligodendrocytes and activated microglia ( Domercq & Matute, 1999 Xin, Weng, & Dougherty, 2009). In the brain, EAAT1 and EAAT2 are responsible for majority (> 95%) of the Glu reuptake ( Danbolt, 2001). Moreover, kinetic parameters ( K m and V max) of these transporters are influenced largely by pH, posttranslational modifications, accessibility on the plasma membrane, and scaffold proteins ( Beart & O’Shea, 2007 Gegelashvili & Schousboe, 1998 Grewer et al., 2014). Glu is cotransported along with sodium ions across the membrane via facilitated diffusion across the electrochemical gradient of sodium. The main driving force for the transport of Glu molecules is the Na +/K + gradient established primarily by the Na +/K + ATPase pump ( Danbolt, 2001 Grewer, Gameiro, & Rauen, 2014). Although the latter group of transporters favors the transport of neutral amino acids, they can transport protonated Glu molecules under acidic conditions. The SLC1A genes encode for seven high-affinity Glu transporters: EAAT1-5 (excitatory amino acid transporters Arriza, Eliasof, Kavanaugh, & Amara, 1997 Fairman, Vandenberg, Arriza, Kavanaugh, & Amara, 1995 Kanai & Hediger, 1992 Pines et al., 1992 Storck, Schulte, Hofmann, & Stoffel, 1992) and ASCT1-2 (alanine/serine/cysteine transporters Arriza et al., 1993 Utsunomiya-Tate, Endou, & Kanai, 1996). Majority of the Glu uptake is performed by the Na +-dependent SLC1A family of Glu transporters ( Gegelashvili, Robinson, Trotti, & Rauen, 2001). Kerr, in Advances in Pharmacology, 2016 2.1 Glutamate Transporters

Transporter 5