Regionally specific expression of high-voltage-activated calcium channels in thalamic nuclei of epileptic and non-epileptic rats
Regionally specific expression of high-voltage-activated calcium channels in thalamic nuclei of epileptic and non-epileptic rats
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DOI：
10.1016/j.mcn.2014.06.005
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发表时间：
2014-07-01
影响因子：
3.5
通讯作者：
Budde, Thomas
中科院分区：
文献类型：
--
作者：
Kanyshkova, Tatyana;Ehling, Petra;Budde, Thomas
广泛性失神癫痫的多基因起源导致离子通道功能障碍，从而允许从生理上的异步活动切换到病理生理上的高度同步的网络活动。来自大鼠和小鼠失神癫痫模型的证据表明，钙通道活性的改变有助于细胞和网络的改变，从而导致癫痫发作活动。在生理环境下，高电压激活(HVA)的钙通道在决定丘脑放电过程中起着重要作用。在这里，我们使用失神癫痫的啮齿动物遗传模型来研究HVA通道对癫痫表型的可能贡献。本研究记录了癫痫Wistar-albino-Glaxo大鼠(WAG/RiJ)和非癫痫大鼠八月哥本哈根-爱尔兰(ACI)大鼠丘脑外侧膝状体背侧核(DLGN)、丘脑腹底复合体(VB)和丘脑网状核(NRT)三个核团的HVA钙电流。癫痫大鼠dLGN神经元HVA钙电流密度显着高于非癫痫对照组，而丘脑其他区域无明显差异。特异性通道阻滞剂的应用表明，该电流的增加是由L类钙通道引起的。癫痫大鼠dLGN L型电流增加的电生理证据与其特定的L型通道Ca(V)1.3的基因和蛋白表达上调有关。其他HVA钙通道未见明显变化。此外，L钙通道的药理失活导致非癫痫大鼠而不是癫痫大鼠丘脑皮质中继(TC)神经元的放电模式发生改变。虽然HVA钙通道对ACI和WAG/Rij的紧张性和阵发性放电的影响不同，但讨论了Ca(V)1.3表达的增加可能间接有助于增强阵发性放电的稳健性，从而导致失神癫痫的癫痫表型。(C)2014 Elsevier Inc.保留所有权利。
The polygenic origin of generalized absence epilepsy results in dysfunction of ion channels that allows the switch from physiological asynchronous to pathophysiological highly synchronous network activity. Evidence from rat and mouse models of absence epilepsy indicates that altered Ca2+ channel activity contributes to cellular and network alterations that lead to seizure activity. Under physiological circumstances, high voltage-activated (HVA) Ca2+ channels are important in determining the thalamic firing profile. Here, we investigated a possible contribution of HVA channels to the epileptic phenotype using a rodent genetic model of absence epilepsy. In this study, HVA Ca2+ currents were recorded from neurons of three different thalamic nuclei that are involved in both sensory signal transmission and rhythmic-synchronized activity during epileptic spike-and-wave discharges (SWD), namely the dorsal part of the lateral geniculate nucleus (dLGN), the ventrobasal thalamic complex (VB) and the reticular thalamic nucleus (NRT) of epileptic Wistar Albino Glaxo rats from Rijswijk (WAG/Rij) and non-epileptic August Copenhagen Irish (ACI) rats. HVA Ca2+ current densities in dLGN neurons were significantly increased in epileptic rats compared with non-epileptic controls while other thalamic regions revealed no differences between the strains. Application of specific channel blockers revealed that the increased current was carded by L-type Ca2+ channels. Electrophysiological evidence of increased L-type current correlated with up-regulated mRNA and protein expression of a particular L-type channel, namely Ca(v)1.3, in dLGN of epileptic rats. No significant changes were found for other HVA Ca2+ channels. Moreover, pharmacological inactivation of L-type Ca2+ channels results in altered firing profiles of thalamocortical relay (TC) neurons from non-epileptic rather than from epileptic rats. While HVA Ca2+ channels influence tonic and burst firing in ACI and WAG/Rij differently, it is discussed that increased Ca(v)1.3 expression may indirectly contribute to increased robustness of burst firing and thereby the epileptic phenotype of absence epilepsy. (C) 2014 Elsevier Inc. All rights reserved.