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Connexin36 knockout mice display increased sensitivity to pentylenetetrazol-induced seizure-like behaviors
University of Waikato.
University of Auckland.
Linköping University, Faculty of Health Sciences.
University of Waikato.
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2010 (English)In: BRAIN RESEARCH, ISSN 0006-8993, Vol. 1360, 198-204 p.Article in journal (Refereed) Published
Abstract [en]

Objective: Large-scale synchronous firing of neurons during seizures is modulated by electrotonic coupling between neurons via gap junctions. To explore roles for connexin36 (Cx36) gap junctions in seizures, we examined the seizure threshold of connexin36 knockout (Cx36KO) mice using a pentylenetetrazol (PTZ) model. Methods: Mice (2-3 months old) with Cx36 wildtype (WT) or Cx36KO genotype were treated with vehicle or 10-40 mg/kg of the convulsant PTZ by intraperitoneal injection. Seizure and seizure-like behaviors were scored by examination of video collected for 20 min. Quantitative real-time PCR (QPCR) was performed to measure potential compensatory neuronal connexin (Cx30.2, Cx37, Cx43 and Cx45), pannexin (PANX1 and PANX2) and gamma-aminobutyric acid type A (GABA(A)) receptor alpha 1 subunit gene expression. Results: Cx36KO animals exhibited considerably more severe seizures; 40 mg/kg of PTZ caused severe generalized (andgt;= grade III) seizures in 78% of KO, but just 5% of WT mice. A lower dose of PTZ (20 mg/kg) induced grade II seizure-like behaviors in 40% KO vs. 0% of WT animals. There was no significant difference in either connexin, pannexin or GABA(A) alpha 1 gene expression between WT and KO animals. Conclusion: Increased sensitivity of Cx36KO animals to PTZ-induced seizure suggests that Cx36 gap junctional communication functions as a physiological anti-convulsant mechanism, and identifies the Cx36 gap junction as a potential therapeutic target in epilepsy.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam. , 2010. Vol. 1360, 198-204 p.
Keyword [en]
Epilepsy, Cx36, Gap junction, PTZ, Interneuron
National Category
Engineering and Technology
URN: urn:nbn:se:liu:diva-62753DOI: 10.1016/j.brainres.2010.09.006ISI: 000284252600019OAI: diva2:374201
Available from: 2010-12-03 Created: 2010-12-03 Last updated: 2010-12-03

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