Momiyama T, Ishihara K, Serikawa T, Moritake K, Sasa M
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
Eur J Pharmacol. 1995 Jul 4;280(2):119-23. doi: 10.1016/0014-2999(95)00189-r.
The effects of nicardipine, a Ca2+ channel antagonist, on the abnormal excitability of hippocampal CA3 neurons in spontaneously epileptic rats (SER), a double mutant (zi/zi, tm/tm), were examined to elucidate whether or not the abnormality was due to that of Ca2+ channels. An intracellular recording study was performed using brain slice preparations of SER 12-15 weeks of age, when SER showed both tonic convulsions and absence-like seizures. Bath application of nicardipine (10 nM) completely inhibited the depolarizing shifts lasting for 60-120 ms and accompanying repetitive firings on mossy fiber stimulation in SER. However, this drug did not affect the single action potential induced by the mossy fiber stimulation in CA3 neurons of SER and normal Wistar rats. In the CA3 pyramidal neurons of SER, the Ca2+ spikes induced by the depolarizing pulse applied in the cell in the presence of tetrodotoxin and tetraethylammonium had a different configuration from that in normal Wistar rats. Nicardipine also inhibited the Ca2+ spikes in SER CA3 neurons at a concentration (1 nM) that had no effect on those in normal Wistar rats, while the Ca2+ spikes in Wistar rat CA3 neurons were inhibited by 10 nM nicardipine. These findings suggest that the abnormal excitability of CA3 pyramidal neurons in SER might be attributed to abnormalities of the Ca2+ channels, and that the Ca2+ channel antagonist may be effective as an antiepileptic drug.
为了阐明自发性癫痫大鼠（SER，一种双突变体（zi/zi，tm/tm））海马CA3神经元异常兴奋性是否归因于钙离子通道异常，研究了钙离子通道拮抗剂尼卡地平对其的影响。使用12 - 15周龄SER的脑片标本进行细胞内记录研究，此时SER表现出强直性惊厥和失神样发作。在SER中，浴用尼卡地平（10 nM）完全抑制了持续60 - 120毫秒并伴随苔藓纤维刺激重复性放电的去极化偏移。然而，该药物不影响SER和正常Wistar大鼠CA3神经元中苔藓纤维刺激诱导的单动作电位。在SER的CA3锥体神经元中，在存在河豚毒素和四乙铵的情况下，细胞内施加去极化脉冲诱导的钙离子峰电位与正常Wistar大鼠的不同。尼卡地平在1 nM浓度时就能抑制SER CA3神经元中的钙离子峰电位，而该浓度对正常Wistar大鼠的钙离子峰电位无影响，而Wistar大鼠CA3神经元中的钙离子峰电位在10 nM尼卡地平时被抑制。这些发现表明，SER中CA3锥体神经元的异常兴奋性可能归因于钙离子通道异常，并且钙离子通道拮抗剂可能作为抗癫痫药物有效。
