Functional and pharmacological properties of GABA-mediated inhibition in the human neocortex

This paper describes some functional and pharmacological properties of GABA-mcdiated mechanisms in the human neocortex maintained in vitro in a slice preparation. Neocortical neurons recorded intracellularly under normal conditions generate stimulus-induced and spontaneous potentials that are mediated by the activation of postsynaptic GABA(A) and GABA(B) receptor subtypes. As reported in other species, pharmacological blockade of the GABA(A) receptor makes epileptiform bursts appear in response to extracellular focal stimuli, thus indicating that inhibition mediated through the activation of the GABA(A) receptor exerts an important role in controlling neuronal excitability in the human neocortex. Spontaneous, prolonged epileptiform discharges are recorded when slices are bathed in Mg2+-free medium, Under these experimental conditions GABA(A) receptor mediated potentials occur between epileptiform events; moreover their rate of occurrence decreases shortly before the onset of each discharge. Blockade of GABA(A) receptor mediated potentials during application of Mg2+-free medium (i) prolongs the epileptiform discharges, (ii) increases the amplitude of their field potential DC shifts, and (iii) augments the concomitant decreases in [Ca2+](o) and increases in [K+](o). These findings indicate therefore that GABA(A) receptor mediated inhibitory potentials are operant during Mg2+-free epileptiform activity, and modulate the occurrence of epileptiform discharges. Moreover, they may also play a role in controlling the changes in [Ca2+](o) and [K+](o) that accompany each epileptiform event.