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 GABA_B outward currents, which are not mirrored by any field activity. These GABA_B outward currents still occurred during application of ionotropic glutamatergic antagonists (n = 12 cells) but were blocked by the GABA_B receptor antagonist CGP55845 (n = 7). Our findings show that the transient occurrence of distinct GABA_B outward currents precedes the appearance of 4AP-induced neuronal network synchronization leading to epileptiform activity in the rodent hippocampus in vitro.