Hamidi Shabnam, Avoli Massimo
Montreal Neurological Institute, Department of Neurology & Neurosurgery, McGill University, 3801 University Street, Montréal, QC, H3A 2B4, Canada.
Montreal Neurological Institute, Department of Neurology & Neurosurgery, McGill University, 3801 University Street, Montréal, QC, H3A 2B4, Canada.
Neuropharmacology. 2015 Aug;95:377-87. doi: 10.1016/j.neuropharm.2015.04.015. Epub 2015 Apr 29.
Depolarizing GABAA receptor-mediated currents are contributed by HCO3(-) efflux, and play a role in initiating ictal-like epileptiform events in several cortical structures supporting the view that GABAA receptor signaling actively participates to epileptiform synchronization. We employed here field potential recordings to analyze the effects of the carbonic anhydrase inhibitor acetazolamide (10 μM) on the epileptiform activity generated in vitro by piriform and entorhinal cortices (PC and EC, respectively) during application of the K(+) channel blocker 4-aminopyridine (4AP, 50 μM). Under these experimental conditions ictal- and interictal-like discharges along with high-frequency oscillations (ripples: 80-200 Hz, fast ripples: 250-500 Hz) occurred in these two regions. In both PC and EC, acetazolamide: (i) reduced the duration and the interval of occurrence of ictal discharges along with the associated ripples and fast ripples; (ii) decreased the interval of occurrence of interictal discharges and the rates of associated fast ripples; and (iii) diminished the duration and amplitude of pharmacologically isolated GABAergic events while increasing their interval of occurrence. Our results indicate that acetazolamide effectively controls 4AP-induced epileptiform synchronization in PC and EC. We propose that this action may rest on decreased GABAA receptor-mediated HCO3(-) efflux leading to diminished depolarization of principal cells and, perhaps, of interneurons.
去极化型GABAA受体介导的电流由HCO3(-)外流产生，并在几个皮质结构中引发癫痫样癫痫发作事件，这支持了GABAA受体信号通路积极参与癫痫样同步化的观点。我们在此采用场电位记录来分析碳酸酐酶抑制剂乙酰唑胺（10 μM）对在应用钾通道阻滞剂4-氨基吡啶（4AP，50 μM）期间梨状皮质和内嗅皮质（分别为PC和EC）体外产生的癫痫样活动的影响。在这些实验条件下，这两个区域出现了癫痫样和发作间期样放电以及高频振荡（涟漪：80 - 200 Hz，快速涟漪：250 - 500 Hz）。在PC和EC中，乙酰唑胺：（i）减少了癫痫样放电的持续时间和发生间隔以及相关的涟漪和快速涟漪；（ii）降低了发作间期放电的发生间隔和相关快速涟漪的频率；（iii）减少了药理学分离的GABA能事件的持续时间和幅度，同时增加了它们的发生间隔。我们的结果表明，乙酰唑胺有效地控制了4AP诱导的PC和EC中的癫痫样同步化。我们提出，这种作用可能基于GABAA受体介导的HCO3(-)外流减少，导致主细胞以及可能的中间神经元去极化减弱。
