RGD Reference Report - Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain. - Rat Genome Database

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Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain.

Authors: Notomi, T  Shigemoto, R 
Citation: Notomi T and Shigemoto R, J Comp Neurol. 2004 Apr 5;471(3):241-76.
RGD ID: 9686394
Pubmed: PMID:14991560   (View Abstract at PubMed)
DOI: DOI:10.1002/cne.11039   (Journal Full-text)

Hyperpolarization-activated cation currents (I(h)) contribute to various physiological properties and functions in the brain, including neuronal pacemaker activity, setting of resting membrane potential, and dendritic integration of synaptic input. Four subunits of the Hyperpolarization-activated and Cyclic-Nucleotide-gated nonselective cation channels (HCN1-4), which generate I(h), have been cloned recently. To better understand the functional diversity of I(h) in the brain, we examined precise immunohistochemical localization of four HCNs in the rat brain. Immunoreactivity for HCN1 showed predominantly cortical distribution, being intense in the neocortex, hippocampus, superior colliculus, and cerebellum, whereas those for HCN3 and HCN4 exhibited subcortical distribution mainly concentrated in the hypothalamus and thalamus, respectively. Immunoreactivity for HCN2 had a widespread distribution throughout the brain. Double immunofluorescence revealed colocalization of immunoreactivity for HCN1 and HCN2 in distal dendrites of pyramidal cells in the hippocampus and neocortex. At the electron microscopic level, immunogold particles for HCN1 and HCN2 had similar distribution patterns along plasma membrane of dendritic shafts in layer I of the neocortex and stratum lacunosum moleculare of the hippocampal CA1 area, suggesting that these subunits could form heteromeric channels. Our results further indicate that HCNs are localized not only in somato-dendritic compartments but also in axonal compartments of neurons. Immunoreactivity for HCNs often occurred in preterminal rather than terminal portions of axons and in specific populations of myelinated axons. We also found HCN2-immunopositive oligodendrocytes including perineuronal oligodendrocytes throughout the brain. These results support previous electrophysiological findings and further suggest unexpected roles of I(h) channels in the brain.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
axon  IDA 9686394 RGD 
dendrite  IDA 9686394 RGD 
neuronal cell body  IDA 9686394; 9686394 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hcn3  (hyperpolarization-activated cyclic nucleotide-gated potassium channel 3)
Hcn4  (hyperpolarization activated cyclic nucleotide-gated potassium channel 4)


Additional Information