Hippocampal seizures alter the expression of the pannexin and connexin transcriptome.
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 Co(2+). 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 Co(2+) treatment. No changes were observed in the presence of tetrodotoxin, indicating that seizure activity is required for these alterations in expression, rather than the Co(2+) 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.
Mylvaganam
Shanthini
S
Division of Fundamental Neurobiology, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada.
Zhang
Liang
L
Wu
Chiping
C
Zhang
Zhang Jane
ZJ
Samoilova
Marina
M
Eubanks
James
J
Carlen
Peter L
PL
Poulter
Michael O
MO
D000818:Animals; D018031:Connexin 43 / Q000096:biosynthesis / Q000235:genetics; D017630:Connexins / Q000096:biosynthesis* / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D012640:Seizures / Q000235:genetics* / Q000378:metabolism*
D018031:Connexin 43; D017630:Connexins; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; C516139:Panx2 protein, mouse