Potassium, pentylenetetrazol, and anticonvulsants in mouse hippocampal slices

We studied the effect of varying potassium (K+) concentrations on spontaneous and pentylenetetrazol (PTZ)-induced population burst discharges in mouse hippocampal slices. Standard techniques were used to obtain extracellular recordings in the CA3 region of hippocampal slices from Swiss-Webster mice (21-28 days old). No spontaneous burst discharges occurred at 3.25 mM K+, but population bursts were observed in 20 and 90% of the slices at 6.25 and 9.25 mM K+, respectively. In the presence of 3.25 mM K+, PTZ produced bursts in 12% of the slices at a concentration of 200 micrograms/ml, in 36% at 300 micrograms/ml, and in 40% at 400 micrograms/ml. Slices exhibiting no burst discharges in the presence of 6.25 mM K+ could be induced to do so with the addition of PTZ; bursts were produced in 11% of these slices at a PTZ concentration of 100 micrograms/ml, in 65% at 150 micrograms/ml, and in 87% at 200 micrograms/ml. The PTZ-induced bursting activity was reversible. Clonazepam abolished the bursting elicited with 200 micrograms/ml PTZ at 6.25 mM K+, and phenytoin reduced, but did not stop, bursting activity. Ethosuximide (ETH) was ineffective in stopping or reducing the burst discharges at a concentration of 125 micrograms/ml ETH was there a consistent reduction in the frequency of population bursts. The induction of PTZ discharges in the hippocampal in vitro preparation offers the advantage of a simplified model for studying the pharmacology of antiepileptic drugs.