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

Epilepsia. 2010 Aug;51(8):1624-7. doi: 10.1111/j.1528-1167.2010.02554.x.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cyclic Nucleotide-Gated Cation Channels / deficiency*
  • Disease Models, Animal
  • Hindlimb / drug effects
  • Hindlimb / physiopathology
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Kindling, Neurologic / genetics
  • Kindling, Neurologic / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscarinic Agonists / adverse effects
  • Pilocarpine / adverse effects
  • Potassium Channels / deficiency*
  • Seizures / chemically induced
  • Seizures / genetics*
  • Seizures / mortality*
  • Seizures / physiopathology*
  • Severity of Illness Index


  • Cyclic Nucleotide-Gated Cation Channels
  • HCN1 protein, human
  • Hcn1 protein, mouse
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Muscarinic Agonists
  • Potassium Channels
  • Pilocarpine