22.01 The Control of Excitation and Inhibition

The glutamate and GABA systems control the intricate balance between excitation and inhibition in the central nervous system. Alterations to this homeostasis can have detrimental effects. Too much excitation leads to anxiety, insomnia, restlessness, exaggerated responses, convulsions and death. Too much inhibition, on the other hand, gives way to sedation, depression, ataxia, anaesthesia, coma and death. Glutamate and GABA are amino acid transmitters, their chemical structures differing by one carboxylic acid group. GABA is synthesized from glutamate via decarboxylation.

Glutamate and GABA act at a variety of receptor subtypes, however only the receptors relevant to the action of alcohol will be discussed here. These include the GABA_A and glutamate N-methyl-D-aspartate (NMDA) receptors.

When GABA or its structural analogues bind to the GABA_A receptors, the ligand gated chloride ion channel changes conformation, allowing increased conductance of chloride ions. The equilibrium potential for chloride is close to resting membrane potential, therefore increased chloride conductance stabilises the membrane, thereby reducing membrane excitability.

The glutamate NMDA receptors are similarly significant for their unique properties, they are voltage-dependent ligand-gated ion channels, require binding of the co-agonist glycine for activation, are highly permeable to calcium ions, and play an important role in synaptic plasticity.