Increased seizure severity and seizure‐related death in mice lacking HCN1 channels |
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| Authors: | Bina Santoro Janet Y. Lee Dario J. Englot Sandra Gildersleeve Rebecca A. Piskorowski Steven A. Siegelbaum Melodie R. Winawer Hal Blumenfeld |
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| Affiliation: | 1. Department of Neuroscience, Columbia University, New York, New York, U.S.A.;2. Departments of Neurology, Neurobiology, and Neurosurgery, Yale University, New Haven, Connecticut, U.S.A.;3. Department of Neurology, Gertrude H Sergievsky Center, Columbia University, New York, New York, U.S.A.;4. Department of Pharmacology, Columbia University, New York, New York, U.S.A.;5. Howard Hughes Medical Institute, New York, New York, U.S.A. |
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| Abstract: | 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. |
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| Keywords: | Intrinsic excitability Ih Conductance HCN1 channels Limbic seizures Kindling Pilocarpine |
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