PHARMACOLOGICAL AND ELECTROGRAPHIC PROPERTIES OF EPILEPTIFORM ACTIVITY-INDUCED BY ELEVATED K+ AND LOWERED CA2+ AND MG2+ CONCENTRATION IN RAT HIPPOCAMPAL SLICES
A. Leschinger et al., PHARMACOLOGICAL AND ELECTROGRAPHIC PROPERTIES OF EPILEPTIFORM ACTIVITY-INDUCED BY ELEVATED K+ AND LOWERED CA2+ AND MG2+ CONCENTRATION IN RAT HIPPOCAMPAL SLICES, Experimental Brain Research, 96(2), 1993, pp. 230-240
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.