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PMID: 20384728 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Increased seizure severity and seizure-related death in mice lacking HCN1 channels.

Epilepsia ·Vol. 51 ·No. 8 ·2010-08-00 ·Pages 1624-7

Santoro B, Lee JY, Englot DJ, Gildersleeve S, Piskorowski RA, Siegelbaum SA, Winawer MR, Blumenfeld H

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.

MeSH Terms
Animals Cyclic Nucleotide-Gated Cation Channels/deficiency Disease Models, Animal Hindlimb/drug effects,physiopathology Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Kindling, Neurologic/genetics,physiology Mice Mice, Inbred C57BL Mice, Knockout Muscarinic Agonists/adverse effects Pilocarpine/adverse effects Potassium Channels/deficiency Seizures/chemically induced,genetics,mortality,physiopathology Severity of Illness Index
Chemicals
Cyclic Nucleotide-Gated Cation Channels HCN1 protein, human Hcn1 protein, mouse Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Muscarinic Agonists Potassium Channels Pilocarpine
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Santoro Bina
Department of Neuroscience, Columbia University, New York, New York, USA. [email protected]
Lee Janet Y
Englot Dario J
Gildersleeve Sandra
Piskorowski Rebecca A
Siegelbaum Steven A
Winawer Melodie R
Blumenfeld Hal
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Article Info
Journal
Epilepsia
Abbr.
Epilepsia
ISSN
1528-1167
DOI
10.1111/j.1528-1167.2010.02554.x
Email
[email protected]
Published
2010-08-00
Pages
1624-7
Language
English
Region
United States
NLM ID
2983306R
PMCID
PMC2952649
Subset
IM
Grants
NINDS NIH HHS · P30 NS052519 · United States
NINDS NIH HHS · R01 NS036658-13 · United States
NINDS NIH HHS · NS 050429 · United States
NINDS NIH HHS · K02 NS050429 · United States
NINDS NIH HHS · NS 061991 · United States
NINDS NIH HHS · R01 NS049307 · United States
NINDS NIH HHS · NS 366058 · United States
NINDS NIH HHS · R01 NS036658 · United States
NINDS NIH HHS · R01 NS049307-06 · United States
NINDS NIH HHS · R01 NS049307-05A1 · United States
NINDS NIH HHS · R01 NS036658-12 · United States
NINDS NIH HHS · NS 049307 · United States
NINDS NIH HHS · R01 NS061991-03 · United States
Howard Hughes Medical Institute · United States
NINDS NIH HHS · R01 NS061991 · United States
NINDS NIH HHS · K02 NS050429-05 · United States
NINDS NIH HHS · F30 NS059074 · United States
NINDS NIH HHS · R01 NS061991-04 · United States
External Links
PubMed source DOI: 10.1111/j.1528-1167.2010.02554.x PMC Full Text View journal details
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