Higashima M, Kinoshita H, Koshino Y
Department of Neuropsychiatry, School of Medicine, Kanazawa University, Kanazawa 920, Japan.
Brain Res. 1998 Jan 19;781(1-2):129-36. doi: 10.1016/s0006-8993(97)01222-5.
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.
为了阐明Ca2+通道亚型在癫痫发生中的可能作用，研究人员检测了大鼠海马切片CA1区，观察Ca2+通道阻滞剂对高频电刺激重复后出现的发作样后放电（ADs）的药理作用，以及在荷包牡丹碱存在下单次刺激后群体峰电位的发作间期样爆发的影响。主要阻断T型Ca2+通道的Ni2+和阿米洛利，在足以消除急性分离和培养的海马神经元中此类Ca2+通道的这两种通道阻滞剂浓度下，抑制了ADs中的峰电位数量。另一方面，L型Ca2+通道阻滞剂硝苯地平以及N型Ca2+通道阻滞剂芋螺毒素GVIA对ADs的产生均无任何影响。此外，这些T型、L型和N型通道阻滞剂对荷包牡丹碱诱导的发作间期样癫痫样放电均无任何影响。因此，我们得出结论，T型Ca2+通道的激活与发作间期活动的机制不同，可能在发作样ADs 的产生中起因果作用。
