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Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain.
J Comp Neurol. 2004 Apr 05; 471(3):241-76.JC

Abstract

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.

Authors+Show Affiliations

Division of Cerebral Structure, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan. notomi@nips.ac.jpNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14991560

Citation

Notomi, Takuya, and Ryuichi Shigemoto. "Immunohistochemical Localization of Ih Channel Subunits, HCN1-4, in the Rat Brain." The Journal of Comparative Neurology, vol. 471, no. 3, 2004, pp. 241-76.
Notomi T, Shigemoto R. Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain. J Comp Neurol. 2004;471(3):241-76.
Notomi, T., & Shigemoto, R. (2004). Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain. The Journal of Comparative Neurology, 471(3), 241-76.
Notomi T, Shigemoto R. Immunohistochemical Localization of Ih Channel Subunits, HCN1-4, in the Rat Brain. J Comp Neurol. 2004 Apr 5;471(3):241-76. PubMed PMID: 14991560.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain. AU - Notomi,Takuya, AU - Shigemoto,Ryuichi, PY - 2004/3/3/pubmed PY - 2004/5/5/medline PY - 2004/3/3/entrez SP - 241 EP - 76 JF - The Journal of comparative neurology JO - J. Comp. Neurol. VL - 471 IS - 3 N2 - 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. SN - 0021-9967 UR - https://www.unboundmedicine.com/medline/citation/14991560/Immunohistochemical_localization_of_Ih_channel_subunits_HCN1_4_in_the_rat_brain_ L2 - https://doi.org/10.1002/cne.11039 DB - PRIME DP - Unbound Medicine ER -