Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain

Monteggia, Lisa M.; Eisch, Amelia J.; Tang, Michael; Kaczmarek, Leonard K.; Nestler, Eric J.

doi:10.1016/s0169-328x(00)00155-8

Cited by 206 publications

(207 citation statements)

References 40 publications

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“…High levels of HCN1 mRNA signals were found in the layer V of the neocortex, pyramidal cell layer of the hippocampal CA areas, hilus of the dentate gyrus, Purkinje cell layer of the cerebellum, optic layer of the 31 superior colliculus, oculomotor nuclei, and hypoglossal nucleus (Monteggia et al, 2000;Santoro et al, 2000). Present results of HCN1-LI localization are in good agreement with those results, except for Purkinje cells where we did not find strong immunoreactivity (data not shown).…”

Section: Correlation Between Localization Of Hcn Mrnas and Hcn-lissupporting

confidence: 90%

“…The HCN2 encoding mRNA was strongly expressed in the mitral cell layer of the olfactory bulb, nucleus of the diagnol band, hippocampal CA3 area, thalamic region, subthalamic nucleus, mammillary nuclei, hypoglossal nucleus, trapezoid body and cochlear nuclei (Monteggia et al, 2000;Santoro et al, 2000). In the present study, we found intense HCN2-LI in neuropil of all of these regions.…”

Section: Correlation Between Localization Of Hcn Mrnas and Hcn-lissupporting

confidence: 70%

“…Expression of HCN3 mRNA was generally weak in the brain but prominent in restricted nuclei such as the glomerular layer of the main olfactory bulb, paraventricular supraoptic and mammillary nuclei of the hypothalamus and paraventricular thalamic nucleus (Monteggia et al, 2000). In the present study, HCN3-LI was very strong in these nuclei as well as in the piriform cortex, inferior olivary complex and interpeduncular nuclei.…”

Section: Correlation Between Localization Of Hcn Mrnas and Hcn-lissupporting

confidence: 53%

“…Immunoreactivity for HCN2 has a very widespread distribution throughout the brain. The distribution of HCN-LI is more extensive than that of their mRNAs indicated by previous in situ hybridization studies (Moosmang et al, 1999;Monteggia et al, 2000;Santoro et al, 2000). In many regions, we found a strong overlap among the …”

Section: General Remarkssupporting

confidence: 46%

“…In situ hybridization studies demonstrate that all four HCN isoforms are expressed in the adult mouse and rat brains with different regional expression patterns (Ludwig et al, 1998;Santoro et al, 1998;Moosmang et al, 1999;Monteggia et al, 2000;Santoro et al, 2000;Bender et al, 2001). …”

Section: Discussionmentioning

confidence: 99%

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Immunohistochemical localization of I_h channel subunits, HCN1–4, in the rat brain

Notomi

Shigemoto

2004

J of Comparative Neurology

512

555

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Hyperpolarization‐activated cation currents (Ih) 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 Ih, have been cloned recently. To better understand the functional diversity of Ih 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 Ih channels in the brain. J. Comp. Neurol. 471:241–276, 2004. © 2004 Wiley‐Liss, Inc.

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Section: Correlation Between Localization Of Hcn Mrnas and Hcn-lissupporting

confidence: 90%

Section: Correlation Between Localization Of Hcn Mrnas and Hcn-lissupporting

confidence: 70%

Section: Correlation Between Localization Of Hcn Mrnas and Hcn-lissupporting

confidence: 53%

Section: General Remarkssupporting

confidence: 46%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Immunohistochemical localization of I_h channel subunits, HCN1–4, in the rat brain

Notomi

Shigemoto

2004

J of Comparative Neurology

512

555

View full text Add to dashboard Cite

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HCN1 pathogenic variants associated with childhood epilepsy in a cohort of Chinese patients

Yang,

Kuang,

Liao

et al. 2023

Epileptic Disorders

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ObjectiveHCN ion channel family has a widespread expression in neurons, and recently, increasing studies have demonstrated their roles in epilepsies.MethodsClinical data of the patients were gathered in a retrospective study. Exon sequencing was used for the patients with unexplained recurrent seizures and varying levels of developmental delay.ResultsIn this study, eight de novo variants of HCN1 genes were uncovered in eight patients, including six missense variants, one nonsense variant and one frameshift insertion variant; five of them were reported for the first time. The onset age for eight patients ranges from one month to one year. Their main clinical manifestations are epilepsy and varying degrees of developmental delay, and the main type of seizure is focal secondary generalized tonic–clonic seizure. Importantly, in our study, one case presented with a form of migrating focal seizure that has not been reported in the literature. Seizures from five of the eight children were effectively controlled with antiepileptic drugs including valproic acid, levetiracetam and oxcarbazepine. One child developed normally and four children developed mild delay. One child was treated with topiramate, and the convulsion was partially controlled and showed moderate to severe developmental delay. The antiepileptic treatment failed for the other two children, and the two children were treated with sodium valproate, oxcarbazepine, lamotrigine, chlorbazan, levetiracetam and nitrodiazepam successively, but their convulsions were not controlled and showed moderate to severe developmental delay.SignificanceOur research reported eight variants in HCN1 gene causing epilepsy; among these variants, five variants were never reported before. HCN1‐related epilepsy usually starts infantile period, and focal secondary generalized tonic–clonic seizure is the most common seizure type. Importantly, we reported the case with migrating focal seizure was rarely reported. Our study expanded both genotype and phenotype for HCN1‐related epilepsy.

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I_h “run‐up” in rat neocortical neurons and transiently rat or human HCN1‐expressing HEK293 cells

Battefeld

Bierwirth

et al. 2010

J of Neuroscience Research

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Hyperpolarization-activated cyclic nucleotide-gated ion channels (HCN) are key determinants of CNS functions. Here we describe an increase in hyperpolarization-activated current (I(h)) at the beginning of whole-cell recordings in rat layer 5 cortical neurons. For a closer investigation of this I(h) increase, we overexpressed the predominant layer 5 rat subunit HCN1 in HEK293 cells. We characterized the resulting I(h) in the cell-attached and whole-cell configurations. Breaking into whole-cell configuration led to about a 30% enhancement of rat HCN1-mediated I(h) accompanied by a depolarizing shift in voltage dependence and an accelerated time course of activation. This current enhancement is not species specific; for human HCN1, the current similarly increases in amount and kinetics. Although the changes were bound to cytosolic solution exchange, they were independent of cAMP, ATP, GTP, and the phosphate group donor phosphocreatine. Together, these data provide a characterization of heterologous expression of rat HCN1 and suggest that cytosolic contents suppress I(h). Such a mechanism might constitute a reserve in h-channel function in vivo.

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Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain

Cited by 206 publications

References 40 publications

Immunohistochemical localization of I_h channel subunits, HCN1–4, in the rat brain

Immunohistochemical localization of I_h channel subunits, HCN1–4, in the rat brain

HCN1 pathogenic variants associated with childhood epilepsy in a cohort of Chinese patients

I_h “run‐up” in rat neocortical neurons and transiently rat or human HCN1‐expressing HEK293 cells

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Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain

Cited by 206 publications

References 40 publications

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

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

HCN1 pathogenic variants associated with childhood epilepsy in a cohort of Chinese patients

Ih “run‐up” in rat neocortical neurons and transiently rat or human HCN1‐expressing HEK293 cells

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Immunohistochemical localization of I_h channel subunits, HCN1–4, in the rat brain

Immunohistochemical localization of I_h channel subunits, HCN1–4, in the rat brain

I_h “run‐up” in rat neocortical neurons and transiently rat or human HCN1‐expressing HEK293 cells