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Increased seizure severity and seizure‐related death in mice lacking HCN1 channels
Author(s) -
Santoro Bina,
Lee Janet Y.,
Englot Dario J.,
Gildersleeve Sandra,
Piskorowski Rebecca A.,
Siegelbaum Steven A.,
Winawer Melodie R.,
Blumenfeld Hal
Publication year - 2010
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2010.02554.x
Subject(s) - epilepsy , pilocarpine , neuroscience , forebrain , kindling , temporal lobe , amygdala , hippocampus , seizure threshold , epileptogenesis , epileptic seizure , psychology , kindling model , medicine , endocrinology , anticonvulsant , central nervous system
Summary 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.