van de Bovenkamp-Janssen M C, Scheenen W J J M, Kuijpers-Kwant F J, Kozicz T, Veening J G, van Luijtelaar E L J M, McEnery M W, Roubos E W
Department of Cellular Animal Physiology, Nijmegen Institute for Neurosciences, University of Nijmegen, The Netherlands.
J Neurobiol. 2004 Mar;58(4):467-78. doi: 10.1002/neu.10291.
In the WAG/Rij rat, a model for human absence epilepsy, spike-wave discharges (SWD) and absence epileptic behavior develop after the age of 3 months. The rostral part of the reticular thalamic nucleus (rRTN) is involved in SWD. Ca(2+) channels play a central role in the initiation and maintenance of burst firing activity of thalamic cells. We hypothesize that a changed expression of alpha(1)-subunits of one or more high voltage-activated Ca(2+) channel types in the rRTN underlies the development of SWD. To test this hypothesis we compared 3- and 6-month-old WAG/Rij rats with nonepileptic, age-matched control rats. By immunocytochemistry, the expressions of alpha(1)1.3-, alpha(1)2.1-, alpha(1)2.2-, and alpha(1)2.3-subunits were shown in both strains, demonstrating the presence of Ca(v)1.3, Ca(v)2.1, Ca(v)2.2, and Ca(v)2.3 channels, respectively. Quantification of channel expression indicates that the development of SWD in WAG/Rij rats is concomitant with an increased expression of Ca(v)2.1 channels in the rRTN. These channels are mainly presynaptic, as revealed by double immunofluorescence involving the presynapse marker syntaxin. The mechanism by which this increase could be related to the occurrence of SWD has been discussed.
在人类失神癫痫模型WAG/Rij大鼠中，3月龄后会出现棘波放电（SWD）和失神癫痫行为。丘脑网状核的吻侧部分（rRTN）参与SWD。钙离子通道在丘脑细胞爆发式放电活动的起始和维持中起核心作用。我们推测，rRTN中一种或多种高压激活钙离子通道类型的α(1)亚基表达变化是SWD发生的基础。为验证这一假设，我们将3月龄和6月龄的WAG/Rij大鼠与年龄匹配的非癫痫对照大鼠进行了比较。通过免疫细胞化学方法，在两种品系中均显示了α(1)1.3、α(1)2.1、α(1)2.2和α(1)2.3亚基的表达，分别证明了Ca(v)1.3、Ca(v)2.1、Ca(v)2.2和Ca(v)2.3通道的存在。通道表达的定量分析表明，WAG/Rij大鼠中SWD的发生与rRTN中Ca(v)2.1通道表达增加同时出现。如涉及突触前标记物 syntaxin的双重免疫荧光所示，这些通道主要位于突触前。文中讨论了这种增加可能与SWD发生相关的机制。
