FIGURE 7.

Ionic coupling and mechanism of glutamate transporters. A, glutamate or aspartate transport via the EAATs is coupled to three Na⁺ ions and one H⁺, followed by the countertransport of one K⁺ ion. Binding of Na⁺ and substrate to the EAATs activates a thermodynamically uncoupled Cl⁻ conductance (pink arrow). B, aspartate transport via Glt_Ph is coupled to the cotransport of at least two Na⁺ ions but is not coupled to the movement of either H⁺ or K⁺. Na⁺ and aspartate binding to Glt_Ph increases the uncoupled chloride conductance (pink arrow). C, simplified kinetic model of transport in Glt_Ph. The empty transporter faces the outside of the membrane (4) where it is available to bind Na⁺ and aspartate (1). After a conformational change, the binding site faces the inside of the membrane where Na⁺ and aspartate can dissociate (2). The empty transporter (3) can then return to face the outside of the membrane (4) where it is again available to bind Na⁺ and aspartate. The uncoupled Cl⁻ conductance (gray arrow) in Glt_Ph is observed in the absence of Na⁺ and aspartate, but their presence enhances the conductance.