Contribution of T-type calcium channels to afterdischarge generation in rat hippocampal slices.
To clarify the possible involvement of Ca2+ channel subtypes in epileptogenesis, the CA1 region of rat hippocampal slices was examined for the pharmacological effects of Ca2+ channel blockers on ictal-like afterdischarges (ADs) observed following the repetition of high-frequency electrical stimulation, as well as on interictal-like bursts of population spikes following single stimuli in the presence of bicuculline. Ni2+ and amiloride, which predominantly block T-type Ca2+ channels, suppressed the number of spikes in ADs at concentrations of these two channel blockers sufficient to eliminate this type of Ca2+ channel in acutely dissociated and cultured hippocampal neurons. On the other hand, neither the L-type Ca2+ channel blocker nifedipine nor the N-type Ca2+ channel blocker City, omega-conotoxin GVIA had any effect on the generation of ADs. In addition, none of these T-, L- and N-type channel blockers had any effect on the bicuculline-induced, interictal-like epileptiform discharges. We therefore conclude that the activation of T-type Ca2+ channels, which is distinct from the mechanisms involved in interictal activity, may play a causative role in the generation of ictal-like ADs.
Higashima
M
M
Department of Neuropsychiatry, School of Medicine, Kanazawa University, Kanazawa 920, Japan.
Kinoshita
H
H
Koshino
Y
Y
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D008978:Mollusk Venoms; D010455:Peptides; D000584:Amiloride; D009532:Nickel; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D001640:Bicuculline