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.