Cesium potentiates epileptiform activities induced by bicuculline methiodide in rat neocortex maintained in vitro

Abstract

We report that extracellular application of cesium (Cs+, 3 mM) potentiated the epileptiform discharge evoked by GABAA-receptor antagonist bicuculline methiodide (BMI 50 microM) in rat neocortical slices maintained in vitro. Cs+ changed BMI-induced epileptiform burst of a few hundred milliseconds evoked by extracellular focal stimuli into epileptiform discharge only a few seconds long (1.8-7 s). Moreover, Cs+ induced the appearance of spontaneously occurring epileptiform activities (0.038-0.15 Hz). Simultaneous intracellular/extracellular recordings indicated that each intracellular epileptiform burst was correlated with a field discharge. Variation of the membrane potential modified only the amplitude of the epileptiform burst and did not alter its frequency of occurrence, indicating that each discharge was a synchronous population event. The epileptiform discharges were not blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP 5-10 microM). In contrast, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX 0.5-5 microM) greatly reduced the duration of each epileptiform discharge by abolishing its afterdischarges in a concentration-dependent manner. This reduction in duration was accompanied by an increase in frequency of occurrence, however. After blockade of non-NMDA receptors with CNQX, a CPP-sensitive spontaneous discharge could be observed. These findings indicate that the inorganic cation Cs+ applied extracellularly can induce spontaneously occurring epileptiform activities in BMI-treated neocortical slices. In addition, receptors of excitatory amino acids play a major role in synchronizing this type of Cs+/BMI-induced spontaneous epileptiform activities.