Transcriptional Upregulation of Cav3.2 Mediates Epileptogenesis in the Pilocarpine Model of Epilepsy

Albert J Becker; Julika Pitsch; Dmitry Sochivko; Thoralf Opitz; Matthäus Staniek; Chien-Chang Chen; Kevin P Campbell; Susanne Schoch; Yoel Yaari; Heinz Beck

doi:10.1523/JNEUROSCI.1421-08.2008

Back

Transcriptional Upregulation of Cav3.2 Mediates Epileptogenesis in the Pilocarpine Model of Epilepsy

Journal article

Open access

Peer reviewed

Transcriptional Upregulation of Cav3.2 Mediates Epileptogenesis in the Pilocarpine Model of Epilepsy

Albert J Becker, Julika Pitsch, Dmitry Sochivko, Thoralf Opitz, Matthäus Staniek, Chien-Chang Chen, Kevin P Campbell, Susanne Schoch, Yoel Yaari and Heinz Beck

The Journal of neuroscience, Vol.28(49), pp.13341-13353

12/03/2008

DOI: 10.1523/JNEUROSCI.1421-08.2008

PMID: 19052226

Files and links (1)

url

https://doi.org/10.1523/JNEUROSCI.1421-08.2008View

Published (Version of record) Open Access

Abstract

In both humans and animals, an insult to the brain can lead, after a variable latent period, to the appearance of spontaneous epileptic seizures that persist for life. The underlying processes, collectively referred to as epileptogenesis, include multiple structural and functional neuronal alterations. We have identified the T-type Ca 2+ channel Ca v 3.2 as a central player in epileptogenesis. We show that a transient and selective upregulation of Ca v 3.2 subunits on the mRNA and protein levels after status epilepticus causes an increase in cellular T-type Ca 2+ currents and a transitional increase in intrinsic burst firing. These functional changes are absent in mice lacking Ca v 3.2 subunits. Intriguingly, the development of neuropathological hallmarks of chronic epilepsy, such as subfield-specific neuron loss in the hippocampal formation and mossy fiber sprouting, was virtually completely absent in Ca v 3.2 −/− mice. In addition, the appearance of spontaneous seizures was dramatically reduced in these mice. Together, these data establish transcriptional induction of Ca v 3.2 as a critical step in epileptogenesis and neuronal vulnerability.

plasticity

burst discharge

temporal lobe epilepsy

reorganization

epileptogenesis

channelopathy

Details

Title: Subtitle: Transcriptional Upregulation of Cav3.2 Mediates Epileptogenesis in the Pilocarpine Model of Epilepsy
Creators: Albert J Becker - Departments of
Julika Pitsch - Departments of
Dmitry Sochivko - Epileptology, University of Bonn Medical Center, and
Thoralf Opitz - Epileptology, University of Bonn Medical Center, and
Matthäus Staniek - Epileptology, University of Bonn Medical Center, and
Chien-Chang Chen - Howard Hughes Medical Institute for Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242, and
Kevin P Campbell - Howard Hughes Medical Institute for Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242, and
Susanne Schoch - Departments of
Yoel Yaari - Department of Physiology, Hebrew University–Hadassah School of Medicine, 91120 Jerusalem, Israel
Heinz Beck - Epileptology, University of Bonn Medical Center, and
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.28(49), pp.13341-13353
DOI: 10.1523/JNEUROSCI.1421-08.2008
PMID: 19052226
NLM abbreviation: J Neurosci
ISSN: 0270-6474
eISSN: 1529-2401
Publisher: Society for Neuroscience
Language: English
Date published: 12/03/2008
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984020633002771

Metrics

8 Record Views

172 Times Cited - Web of Science