RGD Reference Report - Loss of HCN1 subunits causes absence epilepsy in rats. - Rat Genome Database

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Loss of HCN1 subunits causes absence epilepsy in rats.

Authors: Nishitani, Ai  Kunisawa, Naofumi  Sugimura, Taketoshi  Sato, Kazuaki  Yoshida, Yusaku  Suzuki, Toshiro  Sakuma, Tetsushi  Yamamoto, Takashi  Asano, Masahide  Saito, Yasuhiko  Ohno, Yukihiro  Kuramoto, Takashi 
Citation: Nishitani A, etal., Brain Res. 2019 Mar 1;1706:209-217. doi: 10.1016/j.brainres.2018.11.004. Epub 2018 Nov 5.
RGD ID: 26923909
Pubmed: PMID:30408474   (View Abstract at PubMed)
DOI: DOI:10.1016/j.brainres.2018.11.004   (Journal Full-text)

Hyperpolarized-activated cyclic nucleotide-gated (HCN) channels underlie hyperpolarization-activated current (Ih) and are involved in controlling the excitability and electrical responsiveness of neurons. Absence epilepsy is clinically defined by a sudden, brief impairment of consciousness and behavioral arrest. Spike-and-wave discharges (SWDs) on electroencephalograms (EEG) are a diagnostic hallmark of absence epilepsy. In rat models of absence epilepsy, impaired function or expression of HCN1, a subtype of HCN channels, has been found. Here, to evaluate whether HCN1 deficiency causes absence epilepsy in rats, we developed Hcn1-knockout rats by transcription activator-like effector nuclease mutagenesis. The cortical and hippocampal pyramidal neurons of these rats displayed a significant reduction of Ih, a pronounced hyperpolarizing shift of the resting membrane potential, and increased input resistance, which indicated that the Hcn1-knockout rats were deficient in HCN1 function. The Hcn1-knockout rats were also more vulnerable to pentylenetetrazol-induced acute convulsions. More importantly, they exhibited spontaneous SWDs, which were accompanied by behavioral arrest, both of which were suppressed by ethosuximide. These results confirm the involvement of the HCN1 subunit in the regulation of input resistance and provide direct evidence that a deficiency of HCN1 caused absence epilepsy in rats.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of membrane hyperpolarization  IMP 26923909 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Objects Annotated

Genes (Rattus norvegicus)
Hcn1  (hyperpolarization-activated cyclic nucleotide-gated potassium channel 1)
Hcn1em1Kyo  (hyperpolarization-activated cyclic nucleotide-gated potassium channel 1; TALEN induced mutant 1, Kyo)

F344-Hcn1em1Kyo  (NA)

Additional Information