Cattani Adriano, Wang Siyan, Lévesque Maxime, Farmer Jean-Pierre, Dudley Roy William Roland, Avoli Massimo
Department of Pediatric Surgery, Division of Neurosurgery, McGill University Health Centre, Montréal, QC, Canada.
Montreal Neurological Institute-Hospital and Departments of Neurology & Neurosurgery, Canada.
Curr Res Neurobiol. 2023 Nov 17;5:100117. doi: 10.1016/j.crneur.2023.100117. eCollection 2023.
The K channel blocker 4-aminopyridine (4AP) has been extensively used to investigate the mechanisms underlying neuronal network synchronization in both and 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 outward currents, which are not mirrored by any field activity. These GABA outward currents still occurred during application of ionotropic glutamatergic antagonists (n = 12 cells) but were blocked by the GABA receptor antagonist CGP55845 (n = 7). Our findings show that the transient occurrence of distinct GABA outward currents precedes the appearance of 4AP-induced neuronal network synchronization leading to epileptiform activity in the rodent hippocampus .
钾通道阻滞剂4-氨基吡啶（4AP）已被广泛用于研究局灶性癫痫的体外和动物模型中神经元网络同步的潜在机制。4AP诱导的效应与兴奋性和抑制性神经递质释放的增加同时出现，但4AP对神经元网络的作用机制仍不清楚。通过对从小鼠（n = 30）获得的急性脑片海马CA3/4锥体层进行同步全细胞膜片钳和场电位记录，我们发现4AP（100μM）诱导的癫痫样放电的出现之前始终会出现假定的GABA外向电流的短暂重现，而任何场活动均未反映出这种电流。这些GABA外向电流在离子型谷氨酸能拮抗剂应用期间（n = 12个细胞）仍然出现，但被GABA受体拮抗剂CGP55845阻断（n = 7）。我们的研究结果表明，在啮齿动物海马中，独特的GABA外向电流的短暂出现先于4AP诱导的神经元网络同步导致癫痫样活动的出现。
