Hyperpolarization-activated and cyclic nucleotide-gated channels are differentially expressed in juxtaglomerular cells in the olfactory bulb of mice

Fried, Hans-Ulrich; Kaupp, U. Benjamin; Müller, Frank

doi:10.1007/s00441-009-0904-9

Cited by 15 publications

(16 citation statements)

References 67 publications

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“…Therefore, the kinetic parameters that we determined suggest that MOB GCs may express a combination HCN1, HCN2, and HCN4 subunits, while HCN3 subunits predominantly contribute to I h in AOB GCs. In agreement with this possibility, all four HCN subunits are expressed in the OB, with HCN1 present in PGCs and GCs (Holderith et al, 2003; Fried et al, 2010), whereas HCN2 to HCN4 are more strongly expressed in the inner layers of the MOB (Notomi and Shigemoto, 2004). In the AOB, HCN1, HCN2, and HCN4 are moderately expressed, while HCN3 exhibits the strongest expression (Notomi and Shigemoto, 2004).…”

Section: Discussionsupporting

confidence: 53%

Hyperpolarization-Activated Currents and Subthreshold Resonance in Granule Cells of the Olfactory Bulb

Ferguson

Whiteus

et al. 2016

eNeuro

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An important contribution to neural circuit oscillatory dynamics is the ongoing activation and inactivation of hyperpolarization-activated currents (Ih). Network synchrony dynamics play an important role in the initial processing of odor signals by the main olfactory bulb (MOB) and accessory olfactory bulb (AOB). In the mouse olfactory bulb, we show that Ih is present in granule cells (GCs), the most prominent inhibitory neuron in the olfactory bulb, and that Ih underlies subthreshold resonance in GCs. In accord with the properties of Ih, the currents exhibited sensitivity to changes in extracellular K+ concentration and ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidin chloride), a blocker of Ih. ZD7288 also caused GCs to hyperpolarize and increase their input resistance, suggesting that Ih is active at rest in GCs. The inclusion of cAMP in the intracellular solution shifted the activation of Ih to less negative potentials in the MOB, but not in the AOB, suggesting that channels with different subunit composition mediate Ih in these regions. Furthermore, we show that mature GCs exhibit Ih-dependent subthreshold resonance in the theta frequency range (4–12 Hz). Another inhibitory subtype in the MOB, the periglomerular cells, exhibited Ih-dependent subthreshold resonance in the delta range (1–4 Hz), while principal neurons, the mitral cells, do not exhibit Ih-dependent subthreshold resonance. Importantly, Ih size, as well as the strength and frequency of resonance in GCs, exhibited a postnatal developmental progression, suggesting that this development of Ih in GCs may differentially contribute to their integration of sensory input and contribution to oscillatory circuit dynamics.

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Section: Discussionsupporting

confidence: 53%

Hyperpolarization-Activated Currents and Subthreshold Resonance in Granule Cells of the Olfactory Bulb

Ferguson

Whiteus

et al. 2016

eNeuro

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“…This result suggests that MEG3, HCN3 and linc01105 regulate the expression of HIF-1α by post-transcriptional mechanisms. Evidence suggests that HIF-1α is expressed in several tumor types as a result of hypoxia and the expression of certain oncogenes3839, and it is involved in cell proliferation4041. Our study suggests that linc01105 influences proliferation by modulating HIF-1α protein expression.…”

Section: Discussionmentioning

confidence: 52%

MEG3, HCN3 and linc01105 influence the proliferation and apoptosis of neuroblastoma cells via the HIF-1α and p53 pathways

Tang

Dong

et al. 2016

Sci Rep

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The purpose of this study was to investigate the differential expression and functional roles of long non-coding RNAs (lncRNAs) in neuroblastoma tissue. LncRNA microarrays were used to identify differentially expressed lncRNAs between tumor and para-tumor tissues. In total, in tumor tissues, 3,098 and 1,704 lncRNAs were upregulated and downregulated, respectively. HCN3 and linc01105 exhibited the higher expression (P < 0.05; P < 0.01, respectively) in neuroblastoma tissue, whereas MEG3 displayed the lower expression (P < 0.01). HIF-1α expression was negatively correlated with cell proliferation in the linc01105 KD group. In addition, Noxa and Bid expression was positively correlated with cell apoptosis. Moreover, linc01105 knockdown promoted cell proliferation, whereas MEG3 overexpression inhibited proliferation. Finally, linc01105 knockdown, MEG3 overexpression and HCN3 knockdown all increased apoptosis. The correlation coefficients between those three lncRNAs and the International Neuroblastoma Staging System (INSS) stage were −0.48, −0.58 and −0.55, respectively. In conclusion, we have identified lncRNAs that are differentially expressed in neuroblastoma tissues. The lncRNAs HCN3, linc01105, and MEG3 may be important in biological behaviors of neuroblastoma through mechanisms involving p53 pathway members such as HIF-1α, Noxa, and Bid. The expressions of MEG3, HCN3 and linc01105 are all negatively correlated with the INSS stage.

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“…However, it is also worth noting that increasing the excitability of the postsynaptic mitral cells by deleting the Kv1.3 Shaker channel resulted in a disturbance of the axonal targeting of presynaptic ORNs (Biju et al 2008). It should be noted that HCN channels are also expressed in both the mitral cells (Angelo & Margrie, 2011) and the juxtaglomerular cells (Holderith et al 2003; Fried et al 2010) of the olfactory bulb, so the morphological changes observed in HCN1 knockout mice (Mobley et al 2010) or in mice in which HCN4 was over‐expressed (e.g. the present study) may result from the malfunctions of any of those cells.…”

Section: Discussionmentioning

confidence: 67%

Hyperpolarisation‐activated cyclic nucleotide‐gated channels regulate the spontaneous firing rate of olfactory receptor neurons and affect glomerular formation in mice

Nakashima

Ishii

Bessho

et al. 2013

The Journal of Physiology

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Key points• Olfactory receptor neurons (ORNs) utilise the spontaneous firing activity for axonal targeting.• Cyclic AMP-gated HCN channels depolarised the membranes of ORNs and enhanced their spontaneous firing activity.• Standing activation of the β-adrenergic receptors maintained the basal cAMP level and resulted in the opening of HCN channels.• The over-expression of HCN4 resulted in a decrease in the number of glomeruli in the olfactory bulb, which was rescued by suppressing HCN4 over-expression.• HCN channels, together with the standing activation of G-protein-coupled receptors, maintained the spontaneous firing activity of ORNs and were essential to glomerular formation in the olfactory bulb.Abstract Olfactory receptor neurons (ORNs), which undergo lifelong neurogenesis, have been studied extensively to understand how neurons form precise topographical networks. Neural projections from ORNs are principally guided by the genetic code, which directs projections from ORNs that express a specific odorant receptor to the corresponding glomerulus in the olfactory bulb. In addition, ORNs utilise spontaneous firing activity to establish and maintain the neural map. However, neither the process of generating this spontaneous activity nor its role as a guidance cue in the olfactory bulb is clearly understood. Utilising extracellular unit-recordings in mouse olfactory epithelium slices, we demonstrated that the hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels in the somas of ORNs depolarise their membranes and boost their spontaneous firing rates by sensing basal cAMP levels; the odorant-sensitive cyclic nucleotide-gated (CNG) channels in cilia do not. The basal cAMP levels were maintained via the standing activation of β-adrenergic receptors. Using a Tet-off system to over-express HCN4 channels resulted in the enhancement of spontaneous ORN activity and dramatically reduced both the size and number of glomeruli in the olfactory bulb. This phenotype was rescued by the administration of doxycycline. These findings suggest that cAMP plays different roles in cilia and soma and that basal cAMP levels in the soma are directly converted via HCN channels into a spontaneous firing frequency that acts as an intrinsic guidance cue for the formation of olfactory networks.

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Hyperpolarization-activated and cyclic nucleotide-gated channels are differentially expressed in juxtaglomerular cells in the olfactory bulb of mice

Cited by 15 publications

References 67 publications

Hyperpolarization-Activated Currents and Subthreshold Resonance in Granule Cells of the Olfactory Bulb

Hyperpolarization-Activated Currents and Subthreshold Resonance in Granule Cells of the Olfactory Bulb

MEG3, HCN3 and linc01105 influence the proliferation and apoptosis of neuroblastoma cells via the HIF-1α and p53 pathways

Hyperpolarisation‐activated cyclic nucleotide‐gated channels regulate the spontaneous firing rate of olfactory receptor neurons and affect glomerular formation in mice

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