Send to

Choose Destination
See comment in PubMed Commons below
J Neurosci. 2008 Dec 3;28(49):13341-53. doi: 10.1523/JNEUROSCI.1421-08.2008.

Transcriptional upregulation of Cav3.2 mediates epileptogenesis in the pilocarpine model of epilepsy.

Author information

Departments of Neuropathology, University of Bonn Medical Center, University of Bonn, Bonn, Germany.


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.

[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center