Picrotoxin-induced epileptic activity in hippocampal and neocortical slices (guinea pig): suppression by organic calcium channel blockers

Abstract

Epileptic activity induced by the GABAA receptor antagonist bicuculline is known to be blocked by organic calcium antagonists. To further analyse the mechanism underlying convulsant activity induced by substances reducing GABA-mediated synaptic transmission, the effect of organic calcium channel blockers on epileptic activity induced by the GABAA channel blocker picrotoxin in hippocampal and neocortical slices of guinea pigs were investigated. Verapamil and flunarizine suppressed paroxysmal depolarization shifts (PDS) of single neurons and accompanying epileptic field potentials (EFP). As a measure of drug action the repetition rate of epileptic events were used. The depression down to 10% the initial value (90% depression) is indicated. In the hippocampus verapamil suppressed PDS/EFP within 70 +/- 16 min (40 mumol/l) and within 39 +/- 5 min (60 mumol/l). This suppression was reversible with washout of verapamil. Flunarizine irreversibly blocked EFP/PDS within 108 +/- 14 min (18 mumol/l). In the neocortex verapamil reversibly suppressed EFP within 146 +/- 6 min (40 mumol/l) and 127 +/- 26 min (60 mumol/l). Flunarizine irreversibly blocked EFP within 181 +/- 30 min (3 mumol/l) and 109 +/- 13 min (18 mumol/l). The results suggest that voltage dependent calcium channels are essentially involved in picrotoxin-induced epileptic activity.