Figure 2.

Possible pathways of GABA release from astrocytes. (A) GABA can be released via a Ca²⁺-activated anion channel (for example Bestrophin 1, Best1, [23]). The driving force for GABA release is the transmembrane GABA gradient. Best1 opening and conductance is controlled by [Ca²⁺]_i. Note that Best1 is also permeable for Cl⁻ and glutamate. (B) GABA transporter (GAT3) operating in reverse mode can release GABA [20]. In addition to the GABA gradient, the transmembrane gradients of Na⁺ (quadratic impact) and Cl⁻ determine the electromotive driving force and, in turn, the direction of GABA transport. (C) The GAT reversal potentials depend on the [GABA]_o. To calculate GAT reversal potential, following values have been taken: [Na⁺]_o = 140 mM, [Cl⁻]_i = 135 mM, [Na⁺]_i = 15 mM, [Cl⁻]_i = 40 mM, and [GABA]_i = 1 mM. The reported [GABA]_o of 0.2 µM in the cortex [40] and 0.8 µM in the hippocampus [41] favor the GAT3-mediated release under resting conditions in the former (GAT_rev ~ −70 mV) but not in the latter (GAT_rev ~ −35 mV). (D) To change the direction of GAT-mediated transport in the hippocampus, either [Na⁺]_i has to be increased to about 25–30 mM (gray arrow; for instance, as a result of EAAT-mediated glutamate uptake [21]) or [GABA]_i, it has to be elevated to about 4 mM (dashed arrow) [28].