ABSTRACT
The amino acid glutamate is the major excitatory neurotransmitter in the central nervous system (CNS) (Collingridge and Lester, 1989; Fonnum, 1984; Ottersen and Storm-Mathisen, 1984). It is released Ca2-dependently by exocytosis from both neurons and astrocytes (Bezzi et al., 1998). In addition, both neurons and glial cells can release glutamate in Ca2-independent ways (Nicholls and Attwell, 1990; Szatkowski et al., 1990; Jabaudon et al., 1999). Glutamate in the extracellular fluid acts on glutamate receptors in the plasma membrane of neurons (Ozawa et al., 1998) and glial cells (Steinhäuser and Gallo, 1996). Glutamate must be removed rapidly from the extracellular fluid so that the stimulation of glutamate receptors reflects release. In addition, prolonged exposure of neurons to high concentrations of glutamate is harmful (Choi et al., 1987). Since there are no extracellular enzymes that can metabolise glutamate, removal of glutamate from the extracellular fluid must be mediated by uptake into surrounding cells. Glutamate transporters are membrane proteins localised in both neurons and glial cells (for review, see Danbolt, 1994; Danbolt et al., 1998). They use the transmembrane electrochemical gradients of Na, K and H to drive the uptake of glutamate into the cell (Billups et al., 1998a), thereby helping to terminate excitatory synaptic transmission and preventing the extracellular glutamate concentration from rising to toxic levels.
