Contribution of L-type calcium channels to epileptiform activity in hippocampal and neocortical slices of guinea-pigs.
The aim of the present investigation was to compare the antiepileptic efficacy of the specific L-type calcium channel blocker nifedipine in hippocampal and neocortical slice preparations in the Mg2+-free model of epilepsy. The main findings were as follows. (1) In hippocampal slices, in general, nifedipine (20-80 micromol/l) exerted a suppressive effect both on repetition rate and on area under epileptiform field potentials. This effect was clearly dose dependent. In the majority of cases, this suppression was preceded by an increase, which was transient in nature. Only in the lowest concentration (20 micromol/l) used, in normal K+, instead of a depression, a persistent increase occurred. (2) In neocortical slices, in the majority of experiments, nifedipine (20-80 micromol/l) showed a depressive action only on the area under the epileptiform field potentials. The depressive effect of nifedipine on the area was dose dependent, although to a lesser extent than in the hippocampus. In nearly half of the slices this suppression was preceded by a transient increase. By contrast, the repetition rate of epileptiform field potentials increased transiently in about 20% of the slices followed by a decrease. In the remaining 80% of the slices the repetition rate increased persistently. (3) An elevation of the K+ concentration accentuated the depressive actions of nifedipine only in the hippocampus. In contrast to elevated K+, in both the hippocampus and the neocortex, epileptiform field potentials were not suppressed in all experiments in normal K+. (4) The reversibility of the depressive effects of nifedipine was differential in the two tissue types. In the hippocampus, after suppression of epileptiform field potentials they reappeared in the overwhelming majority of slices. In the neocortex, this was the case in only one experiment. These findings may indicate the existence of L-type calcium channels with a differential functional significance for epileptogenesis and/or the existence of different forms of L-type channels in hippocampal and neocortical tissue. As a whole, the differential effects of L-type calcium channel blockade in the hippocampus and neocortex point to differences in the network properties of the two tissue types.
Straub
H
H
Institut für Physiologie, Universität Münster, Germany.
Köhling
R
R
Frieler
A
A
Grigat
M
M
Speckmann
E J
EJ
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000503:physiopathology*; D005260:Female; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D019579:Neocortex / Q000187:drug effects / Q000503:physiopathology*; D009543:Nifedipine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009543:Nifedipine