Reciprocal regulation of epileptiform neuronal oscillations and electrical synapses in the rat hippocampus.

Erika R Kinjo,Guilherme S V Higa,Alexandre H Kihara,Edgard Morya,Angela C Valle,Luiz R G Britto,Stéphane Charpier

doi:10.1371/journal.pone.0109149

Erika R Kinjo, Guilherme S V Higa + Show 5 more

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https://doi.org/10.1371/journal.pone.0109149

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Journal: PloS one	Publication Date: Oct 9, 2014
Citations: 13	License type: CC BY 4.0

Affiliation: Universidade Federal do ABC, Universidade de São Paulo

Abstract

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.

Highlights

Gap junction (GJ) channels couple adjacent cells, allowing transfer of second messengers, ions, and molecules up to 1 kDa
Once we determined that GJ communication is involved in the epileptiform activity induced by pilocarpine and that Cxs undergo alterations in gene expression and posttranslational modifications, we focused on Cx distribution in CA3
The main purposes of this work were to demonstrate the involvement of GJ communication in the epileptiform activity and the possible alterations in Cx gene expression, protein levels, phosphorylation profile and distribution in the hippocampus triggered by pilocarpine

Summary

Introduction

Gap junction (GJ) channels couple adjacent cells, allowing transfer of second messengers, ions, and molecules up to 1 kDa. At least 20 Cx genes were identified in the mouse and human genome [1]. Several evidences from animal models [5,6,7,8,9,10,11] and human slices from epileptic patients [12,13] indicate the participation of GJ channels in the generation and maintenance of epileptic seizures. Specific alterations of Cx expression have been described in tissue from epileptic patients [14,15,16] and in experimental models [11,17,18,19,20]

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