4-Aminopyridine induces a long-lasting depolarizing GABA-ergic potential in human neocortical and hippocampal neurons maintained in vitro.

Neocortical or hippocampal neurons were recorded intracellularly in slices obtained from human epileptogenic brain tissue excised during surgical treatment of epilepsy and perfused with medium containing 4-aminopyridine (4-AP, 50 microM). In addition to spontaneously occurring excitatory and inhibitory postsynaptic potentials, most of the neurons generated a long-lasting (up to 1.5 s) depolarization (LLD) which: (i) behaved as expected for a synaptic potential when the resting membrane potential was varied with intracellular injection of depolarizing and hyperpolarizing current; (ii) exerted a shunting inhibitory action on the generation of action potentials induced by intracellular depolarizing current pulses; and (iii) was blocked by bath application of bicuculline methiodide. It is concluded that like pyramidal or granule cells in the rat hippocampal slice, human neocortical and hippocampal cells possess in the presence of 4AP the ability to generate a LLD which is mediated through GABAA receptors presumably located into the dendrites.