Increased seizure severity and seizure-related death in mice lacking HCN1 channels
Version of Record online: 2 APR 2010
Wiley Periodicals, Inc. © 2010 International League Against Epilepsy
Volume 51, Issue 8, pages 1624–1627, August 2010
How to Cite
Santoro, B., Lee, J. Y., Englot, D. J., Gildersleeve, S., Piskorowski, R. A., Siegelbaum, S. A., Winawer, M. R. and Blumenfeld, H. (2010), Increased seizure severity and seizure-related death in mice lacking HCN1 channels. Epilepsia, 51: 1624–1627. doi: 10.1111/j.1528-1167.2010.02554.x
- Issue online: 5 AUG 2010
- Version of Record online: 2 APR 2010
- Accepted February 3, 2010; Early View publication April 2, 2010.
- Intrinsic excitability;
- Ih Conductance;
- HCN1 channels;
- Limbic seizures;
Persistent down-regulation in the expression of the hyperpolarization-activated HCN1 cation channel, a key determinant of intrinsic neuronal excitability, has been observed in febrile seizure, temporal lobe epilepsy, and generalized epilepsy animal models, as well as in patients with epilepsy. However, the role and importance of HCN1 down-regulation for seizure activity is unclear. To address this question we determined the susceptibility of mice with either a general or forebrain-restricted deletion of HCN1 to limbic seizure induction by amygdala kindling or pilocarpine administration. Loss of HCN1 expression in both mouse lines is associated with higher seizure severity and higher seizure-related mortality, independent of the seizure-induction method used. Therefore, down-regulation of HCN1 associated with human epilepsy and rodent models may be a contributing factor in seizure behavior.