van Luijtelaar G, Wiaderna D, Elants C, Scheenen W
NICI, Department of Comparative and Physiological Psychology, Psychology Laboratory, Nijmegen University, PO Box 9104, 6500 HE, Nijmegen, Netherlands.
Eur J Pharmacol. 2000 Oct 20;406(3):381-9. doi: 10.1016/s0014-2999(00)00714-7.
The role of the T-type Ca(2+) channel blocker, ethosuximide, the L-type Ca(2+) channel blocker, nimodipine and L-type Ca(2+) channel opener, BAY K8644 (1,4 Dihydro-2, 6-dimethyl-5-nitro-4-[trifluoromethyl)-phenyl]-3-pyridine carboxylic acid methyl ester), was investigated on spike-wave discharges in WAG/Rij rats. This strain is considered as a genetic model for generalized absence epilepsy. A dose-dependent decrease in the number of spike-wave discharges was found after i.c.v. ethosuximide, an increase after i.p. nimodipine and a decrease after i.c.v. BAY K8644. BAY K8644 was also able to antagonise the effects of nimodipine. Preliminary data were obtained with two conotoxins, MVIIC and GVIA, which block P/Q-type and N-type Ca(2+) channels, respectively. Only after i.c.v. administration of omega-conotoxin GVIA were the number and duration of spike-wave discharges reduced, but animals showed knock-out lying. The latter suggests behavioural or toxic effects and that the decrease in spike-wave activity cannot unequivocally be attributed to blockade of N-type Ca(2+) channels. It can be concluded that T- and L-type Ca(2+) channel blockers show opposite effects on spike-wave discharges. Furthermore, these effects are difficult to explain in terms of a model for spindle burst activity in thalamic relay cells proposed by McCormick and Bal [Sleep and arousal: thalamocortical mechanisms.
研究了T型钙通道阻滞剂乙琥胺、L型钙通道阻滞剂尼莫地平和L型钙通道开放剂BAY K8644（1,4-二氢-2,6-二甲基-5-硝基-4-[三氟甲基）-苯基]-3-吡啶羧酸甲酯）对WAG/Rij大鼠棘波放电的作用。该品系被认为是全身性失神癫痫的遗传模型。脑室内注射乙琥胺后，棘波放电次数呈剂量依赖性减少，腹腔注射尼莫地平后增加，脑室内注射BAY K8644后减少。BAY K8644也能够拮抗尼莫地平的作用。用两种芋螺毒素MVIIC和GVIA获得了初步数据，它们分别阻断P/Q型和N型钙通道。仅在脑室内注射ω-芋螺毒素GVIA后，棘波放电的次数和持续时间减少，但动物出现敲除性躺卧。后者提示有行为或毒性作用，且棘波活动的减少不能明确归因于N型钙通道的阻断。可以得出结论，T型和L型钙通道阻滞剂对棘波放电表现出相反的作用。此外，根据麦科米克和巴尔提出的丘脑中继细胞纺锤体爆发活动模型，这些作用难以解释[睡眠与觉醒：丘脑皮质机制。
