GABAB receptor outward currents are transiently disclosed by the convulsant 4-aminopyridine in vitro

Abstract

The K+ channel blocker 4-aminopyridine (4AP) has been extensively used to investigate the mechanisms underlying neuronal network synchronization in both in vitro and in vivo animal models of focal epilepsy. 4AP-induced effects are paralleled by an increase in both excitatory and inhibitory neurotransmitter release, but the mechanisms of action of 4AP on neuronal networks remain unclear. By employing simultaneous whole-cell patch clamp and field potential recordings from hippocampal CA3/4 pyramidal layer of acute brain slices obtained from mice (n = 30), we found that the appearance of epileptiform discharges induced by 4AP (100 μM) is consistently preceded by the transient recurrence of presumptive GABAB outward currents, which are not mirrored by any field activity. These GABAB outward currents still occurred during application of ionotropic glutamatergic antagonists (n = 12 cells) but were blocked by the GABAB receptor antagonist CGP55845 (n = 7). Our findings show that the transient occurrence of distinct GABAB outward currents precedes the appearance of 4AP-induced neuronal network synchronization leading to epileptiform activity in the rodent hippocampus in vitro.