Convulsant actions of 4-aminopyridine on the guinea-pig olfactory cortex slice

The effects of bath-applied 4-aminopyridine on neurones and extracellular potassium and calcium concentrations were recorded in slices of guinea-pig olfactory cortex. Neurones were orthodromically activated by stimulating the lateral olfactory tract. 4-Aminopyridine (3-10 microM) had the following effects: (1) an increase in the frequency and amplitude of spontaneous postsynaptic potentials; (2) a prolongation and oscillatory behaviour of orthodromically evoked postsynaptic potentials; (3) induction of spontaneous or stimulus-evoked seizure-type discharges which were accompanied by large rises in extracellular potassium and falls in calcium concentration; (4) a prolongation of the lateral olfactory tract population fibre spike. Prior to paroxysmal depolarization, membrane potential, input resistance and soma spike duration were unaffected. In the seconds before seizure discharges, a late hyperpolarizing potential (evoked by orthodromic stimulation) was reduced in amplitude or abolished. Diphenylhydantoin (50 microM) or magnesium ions (5 mM) prevented paroxysmal activity. Our results show that 4-aminopyridine can produce seizure-type discharges in a brain slice preparation. The role of increased spontaneous potentials and possible loss of synaptic inhibition as causal factors for such discharges is discussed.