RGD Reference Report - Rapid loss of dendritic HCN channel expression in hippocampal pyramidal neurons following status epilepticus. - Rat Genome Database

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Rapid loss of dendritic HCN channel expression in hippocampal pyramidal neurons following status epilepticus.

Authors: Jung, S  Warner, LN  Pitsch, J  Becker, AJ  Poolos, NP 
Citation: Jung S, etal., J Neurosci. 2011 Oct 5;31(40):14291-5. doi: 10.1523/JNEUROSCI.1148-11.2011.
RGD ID: 9686365
Pubmed: PMID:21976514   (View Abstract at PubMed)
PMCID: PMC3208968   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.1148-11.2011   (Journal Full-text)

Epilepsy is associated with loss of expression and function of hyperpolarization-activated, cyclic nucleotide-gated (HCN) ion channels. Previously, we showed that loss of HCN channel-mediated current (I(h)) occurred in the dendrites of CA1 hippocampal pyramidal neurons after pilocarpine-induced status epilepticus (SE), accompanied by loss of HCN1 channel protein expression. However, the precise onset and mechanistic basis of HCN1 channel loss post-SE was unclear, particularly whether it preceded the onset of spontaneous recurrent seizures and could contribute to epileptogenesis or development of the epileptic state. Here, we found that loss of I(h) and HCN1 channel expression began within an hour after SE and involved sequential processes of dendritic HCN1 channel internalization, delayed loss of protein expression, and later downregulation of mRNA expression. We also found that an in vitro SE model reproduced the rapid loss of dendritic I(h), demonstrating that this phenomenon was not specific to in vivo SE. Together, these results show that HCN1 channelopathy begins rapidly and persists after SE, involves both transcriptional and nontranscriptional mechanisms, and may be an early contributor to epileptogenesis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
status epilepticus  ISOHcn1 (Rattus norvegicus)9686365; 9686365 RGD 
status epilepticus  IEP 9686365 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hcn1  (hyperpolarization-activated cyclic nucleotide-gated potassium channel 1)

Genes (Mus musculus)
Hcn1  (hyperpolarization activated cyclic nucleotide gated potassium channel 1)

Genes (Homo sapiens)
HCN1  (hyperpolarization activated cyclic nucleotide gated potassium channel 1)


Additional Information