Cesium potentiates epileptiform activities induced by bicuculline methiodide in rat neocortex maintained in vitro.
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.
Montreal Neurological Institute, Quebec, Canada.
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D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D002586:Cesium / Q000494:pharmacology*; D004357:Drug Synergism; D004569:Electroencephalography / Q000187:drug effects; D004828:Epilepsies, Partial / Q000139:chemically induced* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects
D000927:Anticonvulsants; D010879:Piperazines; D011810:Quinoxalines; D011963:Receptors, GABA-A; D002586:Cesium; C017069:bicuculline methiodide; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D001640:Bicuculline