Fig. 2. GABAergic signaling in pathological states. (a) In the normal state, GABA binds to the GABAA and GABAB receptor, thereby suppressing postsynaptic neurons. The GABA transporter (GAT) also transfers synaptic and extrasynaptic GABA into astrocytes. (b) If GABAA receptor subunits are mutated, the GABAA receptor cannot be activated appropriately by GABA. Because the GABAA receptor is the player that most affects post-synaptic neurons, mutations of its subunits cause postsynaptic neurons to function abnormally. (c) GABAA and GABAB receptors in the plasma membrane of nerve cells operate over an appropriate density range; as their density decreases, the activity of GABA-bound receptors is decreased and synaptic function become abnormal. (d) Loss of GAT function causes decreased astrocytic uptake of synaptic GABA. This leaves excess eGABA to bind to GABAA and GABAB receptors. As more receptors respond to GABA, inhibitory signaling is increased.
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