Hippocampal seizures alter the expression of the pannexin and connexin transcriptome

• Published in: Journal of neurochemistry Vol. 112; no. 1; pp. 92 - 102
• Main Authors: Mylvaganam, Shanthini, Zhang, Liang, Wu, Chiping, Zhang, Zhang Jane, Samoilova, Marina, Eubanks, James, Carlen, Peter L, Poulter, Michael O
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 2010; Blackwell Publishing Ltd; Wiley-Blackwell
• Subjects: Animals; Biological and medical sciences; Connexin 43 - biosynthesis; Connexin 43 - genetics; connexins; Connexins - biosynthesis; Connexins - genetics; Convulsions & seizures; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; hippocampus; Hippocampus - metabolism; Male; Medical sciences; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Nervous system (semeiology, syndromes); Neurology; Neurons; Neurosciences; pannexins; Proteins; seizures; Seizures - genetics; Seizures - metabolism; transcriptome; Modification; Nervous system diseases; Data analysis; Induction; Epilepsy; pannexins; transcriptome; Central nervous system; Alteration; Gene expression; connexins; Protein; Encephalon; Cerebral disorder; Connexin; Treatment; Convulsion; Gene; Central nervous system disease; seizures; Neurological disorder; Hippocampus
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2009.06431.x

Some forms of seizure activity can be stopped by gap junctional (GJ) blockade. Here, we found that GJ blockers attenuate hippocampal seizure activity induced by a novel seizuregenic protocol using Co²⁺. We hypothesized that this activity may occur because of the altered expression of connexin (Cx) and/or pannexin (Panx) mRNAs and protein. We found a 1.5-, 1.4-, and 2-fold increase in Panx1, Panx2, and Cx43 mRNAs, respectively. Significant post-translational modifications of the proteins Cx43 and Panx1 were also observed after the Co²⁺ treatment. No changes were observed in the presence of tetrodotoxin, indicating that seizure activity is required for these alterations in expression, rather than the Co²⁺ treatment itself. Further analysis of the QPCR data showed that the Cx and Panx transcriptome becomes remarkably re-organized. Pannexin (Panxs 1 and 2) and glial connexin mRNA became highly correlated to one another; suggesting that these genes formed a transcriptomic network of coordinated gene expression, perhaps facilitating seizure induction. These data show that seizure activity up-regulates the expression of both glial and neuronal GJ mRNAs and protein while inducing a high degree of coordinate expression of the GJ transcriptome.