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 effic acy of the specific L-type calcium channel blocker nifedipine in hippocampa l and neocortical slice preparations in the Mg2+-free model of epilepsy. Th e main findings were as follows. (1) In hippocampal slices, in general, nif edipine (20-80 mu mol/l) exerted a suppressive effect both on repetition ra te 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 concentratio n (20 mu mol/l) used, in normal K+, instead of a depression, a persistent i ncrease occurred. (2) In neocortical slices, in the majority of experiments , nifedipine (20-80 mu mol/l) showed a depressive action only on the area u nder the epileptiform field potentials. The depressive effect of nifedipine on the area was dose dependent, although to a lesser extent than in the hi ppocampus. 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 d ecrease. In the remaining 80% of the slices the repetition rate increased p ersistently. (3) An elevation of the K+ concentration accentuated the depre ssive actions of nifedipine only in the hippocampus. In contrast to elevate d K+, in both the hippocampus and the neocortex, epileptiform field potenti als were not suppressed in all experiments in normal K+. (4) The reversibil ity of the depressive effects of nifedipine was differential in the two tis sue types. In the hippocampus, after suppression of epileptiform field pote ntials they reappeared in the overwhelming majority of slices. In the neoco rtex, 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 existe nce of different forms of L-type channels in hippocampal and neocortical ti ssue. As a whole, the differential effects of L-type calcium channel blocka de in the hippocampus and neocortex point to differences in the network pro perties of the two tissue types. (C) 1999 IBRO. Published by Elsevier Scien ce Ltd.