Biochip Center, Department of Basic Medicine, China Medical University, Shenyang 110001, China.
Brain Res Bull. 2013 Jul;96:1-9. doi: 10.1016/j.brainresbull.2013.04.003. Epub 2013 Apr 19.
Voltage-gated sodium channels (VGSCs) play a crucial role in epilepsy. The expressions of different VGSCs subtypes are varied in diverse animal models of epilepsy that may reflect their multiple phenotypes or the complexity of the mechanisms of epilepsy. In a previous study, we reported that NaV1.1 and NaV1.3 were up-regulated in the hippocampus of the spontaneously epileptic rat (SER). In this study, we further analyzed both the expression and distribution of the typical VGSC subtypes NaV1.1, NaV1.2, NaV1.3 and NaV1.6 in the hippocampus and in the cortex of the temporal lobe of two genetic epileptic animal models: the SER and the tremor rat (TRM). The expressions of calmodulin (CaM) and calmodulin-dependent protein kinase II (CaMKII) were also analyzed with the purpose of assessing the effect of the CaM/CaMKII pathway in these two models of epilepsy. Increased expression of the four VGSC subtypes and CaM, accompanied by a decrease in CaMKII was observed in the hippocampus of both the SERs and the TRM rats. However, the changes observed in the expression of VGSC subtypes and CaM were decreased with an elevated CaMKII in the cortex of their temporal lobes. Double-labeled immunofluorescence data suggested that in SERs and TRM rats, the four subtypes of the VGSC proteins were present throughout the CA1, CA3 and dentate gyrus regions of the hippocampus and temporal lobe cortex and these were co-localized in neurons with CaM. These data represent the first evidence of abnormal changes in expression of four VGSC subtypes (NaV1.1, NaV1.2, NaV1.3 and NaV1.6) and CaM/CaMKII in the hippocampus and temporal lobe cortex of SERs and TRM rats. These changes may be involved in the generation of epileptiform activity and underlie the observed seizure phenotype in these rat models of genetic epilepsy.
电压门控钠离子通道（VGSCs）在癫痫中起着至关重要的作用。不同的 VGSCs 亚型在各种癫痫动物模型中的表达不同，这可能反映了它们的多种表型或癫痫机制的复杂性。在之前的研究中，我们报道了自发性癫痫大鼠（SER）海马体中 NaV1.1 和 NaV1.3 的表达上调。在这项研究中，我们进一步分析了两种遗传性癫痫动物模型（SER 和震颤大鼠（TRM））海马体和颞叶皮质中典型 VGSC 亚型 NaV1.1、NaV1.2、NaV1.3 和 NaV1.6 的表达和分布。还分析了钙调蛋白（CaM）和钙调蛋白依赖性蛋白激酶 II（CaMKII）的表达，目的是评估 CaM/CaMKII 通路在这两种癫痫模型中的作用。在 SER 和 TRM 大鼠的海马体中观察到四种 VGSC 亚型和 CaM 的表达增加，同时 CaMKII 减少。然而，在它们颞叶皮质中，观察到 VGSC 亚型和 CaM 的表达变化减少，而 CaMKII 升高。双标记免疫荧光数据表明，在 SER 和 TRM 大鼠中，四种 VGSC 蛋白亚型存在于海马体的 CA1、CA3 和齿状回以及颞叶皮质区域，并且与 CaM 共定位在神经元中。这些数据代表了 SER 和 TRM 大鼠海马体和颞叶皮质中四种 VGSC 亚型（NaV1.1、NaV1.2、NaV1.3 和 NaV1.6）和 CaM/CaMKII 表达异常变化的首次证据。这些变化可能参与了癫痫样活动的产生，并构成了这些遗传性癫痫大鼠模型中观察到的癫痫发作表型的基础。
