Differential involvement of L-type calcium channels in epileptogenesis of rat hippocampal slices during ontogenesis.
Organic calcium channel antagonists block epileptiform activity in adult tissue, suggesting an essential role of L-type channels in epileptogenesis in the mature CNS. By contrast, this remains doubtful for neonatal tissue, as the density of calcium channels changes markedly with ontogenesis. The paper addresses this question by exploring the antiepileptic efficacy of the L-type calcium channel blockers verapamil and nifedipine in low-Mg(2+)-epilepsy in rat hippocampal slices of different postnatal (PN) ages. Field (CA3, CA1) and membrane potentials (CA3) were recorded. Washout of Mg(2+) induced epileptiform potentials, which were blocked age-dependently: Verapamil suppressed activity in all preparations of PN1-5 and PN13-30+, but only in 70% of PN6-12. Nifedipine depressed activity in >75% of slices of PN13-30+, but only in 33% of PN1-12. The findings indicate a role of L-type calcium channels in epileptogenesis from PN13 onwards, with phenylalkylamine-sensitive calcium channels also being involved during PN1-5.
Köhling
R
R
Institut für Physiologie, Robert-Koch-Strasse 27a, Münster, D-48149, Germany.
Straub
H
H
Speckmann
E J
EJ
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology; D004827:Epilepsy / Q000188:drug therapy; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology* / Q000627:therapeutic use; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D014700:Verapamil / Q000494:pharmacology* / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D014700:Verapamil; D009543:Nifedipine