Department of Human Anatomy and Histoembryology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China.
Department of Human Anatomy and Histoembryology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China; Center for Human Assisted Reproduction, Maternity and Child Healthcare Hospital of Shaanxi Province, Xi'an, Shaanxi 710003, China.
Neurochem Int. 2018 Mar;114:108-119. doi: 10.1016/j.neuint.2018.02.005. Epub 2018 Feb 7.
Voltage-dependent calcium channels (VDCC) have been shown to regulate neuronal excitability and their antagonists have been used clinically for the control of seizures. While functional studies of VDCC in epileptogenesis in the CA1 area of hippocampus or the dentate gyrus have been done, few studies were carried out in the CA3 area. Given the bursting characteristics of the CA3 neurons, we speculated that VDCC in the CA3 area might play an important role in the epileptogenesis. In the present study in the mouse pilocarpine model of temporal lobe epilepsy, we investigated the alterations of alpha 1 subunits of L-type VDCC in the CA3 area of the hippocampus at different stages of epileptogenesis, i.e., acute stage from 10 min to 1 day during and after pilocapine-induced status epilepticus (SE), latent period at 1 week, and chronic stage with spontaneous recurrent seizures at 2 months after SE. We found that an immediate redistribution of alpha 1 subunits in the CA3 area occurred during SE which might be involved in the seizure occurrence indicated by the Racine score record. Alterations of alpha 1 subunits were also demonstrated in the latent period and chronic stage, which might be related to the epileptogenesis and occurrence of epilepsy. Ca1.3, but not Ca1.2, was expressed in reactive astrocytes of the CA3 area, indicating the involvement of Ca1.3 in the modulation of astrocytic Ca homeostasis during epileptogenesis.
电压门控钙通道 (VDCC) 已被证明可调节神经元兴奋性,其拮抗剂已在临床上用于控制癫痫发作。虽然已经在海马体 CA1 区或齿状回的癫痫发生中进行了 VDCC 的功能研究,但在 CA3 区进行的研究较少。鉴于 CA3 神经元的爆发特性,我们推测 CA3 区的 VDCC 可能在癫痫发生中发挥重要作用。在本研究中,我们在小鼠匹鲁卡品颞叶癫痫模型中,研究了在癫痫发生的不同阶段,即在匹鲁卡品诱导的癫痫持续状态 (SE) 期间和之后的 10 分钟至 1 天的急性期、1 周的潜伏期以及 SE 后 2 个月出现自发性复发性癫痫的慢性期,海马体 CA3 区 L 型 VDCC 的 alpha 1 亚基的变化。我们发现,在 SE 期间,alpha 1 亚基在 CA3 区立即重新分布,这可能与 Racine 评分记录所示的癫痫发作发生有关。在潜伏期和慢性期也观察到 alpha 1 亚基的改变,这可能与癫痫发生和癫痫发作有关。Ca1.3 而不是 Ca1.2 在 CA3 区的反应性星形胶质细胞中表达,表明 Ca1.3 参与了癫痫发生过程中星形胶质细胞钙稳态的调节。