PHARMACOLOGICAL AND ELECTROGRAPHIC PROPERTIES OF EPILEPTIFORM ACTIVITY-INDUCED BY ELEVATED K+ AND LOWERED CA2+ AND MG2+ CONCENTRATION IN RAT HIPPOCAMPAL SLICES

We studied some of the physiological and pharmacological properties of an in vitro model of epileptic seizures induced by elevation of [K+]0 (to 8 mM and 10 mM) in combination with lowering of [Mg2+]0 (to 1.4 m M and 1.6 mM) and [Ca2+]0 (to 0.7 mM and 1 mM) in rat hippocampal slic es. These concentrations correspond to the ionic constitution of the e xtracellular microenvironment during seizures in vivo. The resulting a ctivity was rather variable in appearance. In area CA3 recurrent disch arges were observed which resulted in seizure-like events with either clonic-like or tonic-clonic-like ictaform events in area CA1. With ion -sensitive electrodes, we measured the field potential and the changes in extracellular ion concentrations which accompany this activity. Th e recurrent discharges in area CA3 were accompanied by small fluctuati ons in [K+]0 and [Ca2+]0. The grouped clonic-like discharges in area C A1 were associated with moderate increases in [K+]0 and small decrease s in [Ca2+]0 in the order of 2 mM and 0.2 mM, respectively. Large, neg ative field-potential shifts and increases in [K+]0 to 13 mM, as well as decreases in [Ca2+]0 by up to 0.4 mM, accompanied the tonic phase o f ictaform events. The ictaform events were not blocked by D-2-aminoph osphonovalerate (2-APV) but were sensitive to 6-cyano-7-nitroquinoxali ne-2,3-dione (CNQX) alone and in combination with 2-APV and ketamine. In order to determine the pharmacological characteristics of the ictaf orm events we bath-applied most clinically employed anticonvulsants (c arbamazepine, phenytoin, valproate, phenobarbital, ethosuximide, trime thadione) and some experimental anticonvulsants (losigamone, vinpoceti ne, and apovincaminic acid). Carbamazepine, phenytoin, valproate, and phenobarbital were effective at clinically relevant doses. The data su ggest that the high-K+ model of epileptiform activity is a good model of focal convulsant activity.