van Luijtelaar E L, Ates N, Coenen A M
NICI, Department of Psychology, University of Nijmegen, The Netherlands.
Epilepsia. 1995 Jan;36(1):86-92. doi: 10.1111/j.1528-1157.1995.tb01671.x.
Old male Wistar rats spontaneously showing hundreds of spike-wave discharges daily were used to investigate the role of calcium ions in nonconvulsive epilepsy. The effects of the L-type calcium channel blocker nimodipine and the L-type channel opener BAY K 8644 on number and duration of these spike-wave discharges were investigated. In rats aged 84-94 weeks standard EEG electrodes were chronically implanted; animals were allowed to recover for 10 days. After a baseline registration, nimodipine 2.2, 8.8, and 35.2 mg/kg or BAY K 8644 in dosages of 0.12, 0.47, and 1.88 mg/kg was administered. A control group received the solvent. EEG recordings were made to evaluate drug effects. The highest dose of nimodipine increased the number of spike-wave discharges, whereas BAY K 8644 reduced the number of spike-wave discharges dose dependently. The highest dose of BAY K 8644 also induced fatal convulsions in 3 animals. Our results demonstrate that the L-type calcium antagonist nimodipine facilitates spike-wave discharges and that the L-type calcium agonist BAY K 8644 protects against these discharges, in contrast to previous results suggesting that calcium channel blockers act as antiepileptic drugs (AEDs) and that calcium channel openers act as convulsants. Our results are a further example of the different pharmacologic profile of convulsive and nonconvulsive epilepsy and are also in contrast to what has been described for T-type calcium channel modulation. We therefore propose that modulation of L-type and T-type calcium channels have opposite effects in nonconvulsive epilepsy.
选用每日自发出现数百次棘波-慢波放电的老年雄性Wistar大鼠，研究钙离子在非惊厥性癫痫中的作用。研究了L型钙通道阻滞剂尼莫地平及L型通道开放剂BAY K 8644对这些棘波-慢波放电的数量和持续时间的影响。在84 - 94周龄的大鼠中，长期植入标准脑电图电极；让动物恢复10天。在进行基线记录后，分别给予2.2、8.8和35.2 mg/kg的尼莫地平或0.12、0.47和1.88 mg/kg剂量的BAY K 8644。对照组给予溶剂。进行脑电图记录以评估药物效果。尼莫地平的最高剂量增加了棘波-慢波放电的数量，而BAY K 8644则剂量依赖性地减少了棘波-慢波放电的数量。BAY K 8644的最高剂量还导致3只动物发生致命性惊厥。我们的结果表明，L型钙拮抗剂尼莫地平促进棘波-慢波放电，而L型钙激动剂BAY K 8644则可防止这些放电，这与之前认为钙通道阻滞剂作为抗癫痫药物（AEDs）且钙通道开放剂作为惊厥剂的结果相反。我们的结果是惊厥性和非惊厥性癫痫不同药理学特征的又一实例，也与T型钙通道调节的描述相反。因此，我们提出L型和T型钙通道的调节在非惊厥性癫痫中具有相反的作用。
