Kinjo Erika R, Higa Guilherme S V, Morya Edgard, Valle Angela C, Kihara Alexandre H, Britto Luiz R G
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, São Paulo, Brazil; Núcleo de Cognição e Sistemas Complexos, Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo, São Paulo, Brazil.
Instituto Internacional de Neurociência de Natal Edmond e Lily Safra, Natal, Rio Grande do Norte, Brazil.
PLoS One. 2014 Oct 9;9(10):e109149. doi: 10.1371/journal.pone.0109149. eCollection 2014.
Gap junction (GJ) channels have been recognized as an important mechanism for synchronizing neuronal networks. Herein, we investigated the participation of GJ channels in the pilocarpine-induced status epilepticus (SE) by analyzing electrophysiological activity following the blockade of connexins (Cx)-mediated communication. In addition, we examined the regulation of gene expression, protein levels, phosphorylation profile and distribution of neuronal Cx36, Cx45 and glial Cx43 in the rat hippocampus during the acute and latent periods. Electrophysiological recordings revealed that the GJ blockade anticipates the occurrence of low voltage oscillations and promotes a marked reduction of power in all analyzed frequencies.Cx36 gene expression and protein levels remained stable in acute and latent periods, whereas upregulation of Cx45 gene expression and protein redistribution were detected in the latent period. We also observed upregulation of Cx43 mRNA levels followed by changes in the phosphorylation profile and protein accumulation. Taken together, our results indisputably revealed that GJ communication participates in the epileptiform activity induced by pilocarpine. Moreover, considering that specific Cxs undergo alterations through acute and latent periods, this study indicates that the control of GJ communication may represent a focus in reliable anti-epileptogenic strategies.
缝隙连接(GJ)通道已被认为是使神经网络同步的重要机制。在此,我们通过分析连接蛋白(Cx)介导的通讯被阻断后的电生理活动,研究了GJ通道在毛果芸香碱诱导的癫痫持续状态(SE)中的作用。此外,我们还检测了大鼠海马在急性期和潜伏期神经元Cx36、Cx45以及胶质细胞Cx43的基因表达调控、蛋白水平、磷酸化谱和分布情况。电生理记录显示,GJ阻断可预见低电压振荡的发生,并促使所有分析频率下的功率显著降低。Cx36基因表达和蛋白水平在急性期和潜伏期保持稳定,而在潜伏期检测到Cx45基因表达上调和蛋白重新分布。我们还观察到Cx43 mRNA水平上调,随后磷酸化谱和蛋白积累发生变化。综上所述,我们的结果无可争议地表明,GJ通讯参与了毛果芸香碱诱导的癫痫样活动。此外,鉴于特定的Cx在急性期和潜伏期会发生改变,本研究表明,控制GJ通讯可能是可靠的抗癫痫策略的一个重点。