Figure 2.

A cartoon illustrating cycling pathways for water, ions and neurotransmitters in a glutamatergic (left) and a GABAergic (right) pre- and post-synaptic neuron pair with an associated astrocyte. In pre-synaptic glutamatergic and GABAergic neurons, action potentials involve serial Na⁺ influx, K⁺ efflux, and Ca²⁺ influx via VGSC, VGPC, and voltage-gated calcium channels (VGCC). After release of pre-synaptic vesicular glutamate (Glu), it binds to post-synaptic ionotropic glutamate receptors (kainateR, AMPAR, NMDAR) or metabotropic glutamate receptors (mGlu), which trigger subsequent Na⁺ and Ca²⁺ influx or Ca²⁺ release from intracellular storage. In contrast, GABA binding leads to a post-synaptic Cl⁻ influx and K⁺ efflux. Glu and GABA are recycled through astrocyte membrane glutamate transports (EAAT) and GABA transporters (GAT) utilizing a Na⁺ gradient via an intermediate glutamine (Gln) step. NKA is the essential enzyme to restore ion gradients in all the processes mentioned above and in all cell compartments. In addition, passive, diffusion-driven components (k_io(p) and k_oi(p)) for water crossing all cell compartment membranes are present (20). As in Fig. 1, AWC perturbations employed in this study are indicated in red. They include extracellular: K⁺ (K_o⁺), TTX_o, DNQX_o plus AP_5,o, kainate_o, PTX_o, and ouabain_o (in (20)). This cartoon is inspired by (60). The abbreviations, definitions and actions of the drugs used are given in Table 1.