Modulation of burst frequency, duration, and amplitude in the zero-Ca2+ model of epileptiform activity

Incubation of hippocampal slices in zero-Ca2+ medium blocks synaptic transm ission and results in spontaneous burst discharges. This seizure-like activ ity is characterized by negative shifts (bursts) in the extracellular field potential and a K+ wave that propagates across the hippocampus. To isolate factors related to seizure initiation, propagation, and termination, a num ber of pharmacological agents were tested. K+ influx and efflux mechanisms where blocked with cesium, barium, tetraethylammonium (TEA), and 4-aminopyr idine (4-AP). The effect of the gap junction blockers, heptanol and octanol , on zero-Ca2+ bursting was evaluated. Neuronal excitability was modulated with tetrodotoxin (TTX), charge screening, and applied electric fields. Gli al cell function was examined with a metabolism antagonist (fluroacetate). Neuronal hyperpolarization by cation screening or applied fields decreased burst frequency but did not affect bunt amplitude or duration. Heptanol att enuated burst amplitude and duration at low concentration (0.2 mM), and blo cked bursting at higher concentration (0.5 mM). CsCl2 (1 mM) had no effect, whereas high concentrations (1 mM) of BaCl2 blocked bursting. TEA (25 mM) and low concentration of BaCl2 (300 mu M) resulted in a two-to sixfold incr ease in burst duration. Fluroacetate also blocked burst activity but only d uring prolonged application (>3 h). Our results demonstrate that burst freq uency, amplitude, and duration can be independently modulated and suggest t hat neuronal excitability plays a central role in burst initiation, whereas potassium dynamics establish burst amplitude and duration.