Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels

A subgroup of cyclic nucleotide-regulated ION CHANNELS of the superfamily of pore-loop cation channels that are opened by hyperpolarization rather than depolarization. The ion conducting pore passes SODIUM, CALCIUM, and POTASSIUM cations with a preference for potassium.

Also Known As:

HCN Pacemaker Channels; HCN1 Channel; HCN2 Channel; HCN2 Potassium Channel; HCN3 Channel; HCN4 Channel; Hyperpolarization Activated Cyclic Nucleotide-Gated Potassium Channel 2; Hyperpolarization Cyclic-Nucleotide Gated Cation Channel 1; Hyperpolarization Cyclic-Nucleotide Gated Cation Channel 3; Hyperpolarization Cyclic-Nucleotide Gated Cation Channel 4; Hyperpolarization-Activated Cation Channel; I(h) Cation Channels; I(h) Channels; Ih Cation Channels; Potassium-Sodium Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2; Cation Channel, Hyperpolarization-Activated; Cation Channels, Ih; Channel, HCN1; Channel, HCN2; Channel, HCN2 Potassium; Channel, HCN3; Channel, HCN4; Channel, Hyperpolarization-Activated Cation; Channels, HCN Pacemaker; Channels, Ih Cation; Hyperpolarization Activated Cation Channel; Hyperpolarization Activated Cyclic Nucleotide Gated Channels; Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 2; Hyperpolarization Cyclic Nucleotide Gated Cation Channel 1; Hyperpolarization Cyclic Nucleotide Gated Cation Channel 3; Hyperpolarization Cyclic Nucleotide Gated Cation Channel 4; Hyperpolarization Cyclic Nucleotide Gated Ion Channels; Pacemaker Channels, HCN; Potassium Channel, HCN2; Potassium Sodium Hyperpolarization Activated Cyclic Nucleotide Gated Channel 2; Hyperpolarization Cyclic-Nucleotide Gated Ion Channels

Networked: 96 relevant articles (4 outcomes, 6 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Amino Acids, Peptides, and Proteins: 1
- Proteins: 484843
  - Carrier Proteins: 12999
    - Membrane Transport Proteins: 589
      - Ion Channels: 6731
        Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: 96
        human HCN1 protein
        human HCN2 protein
        human HCN3 protein
        human HCN4 protein
        mouse Hcn1 protein
        mouse Hcn2 protein
        mouse HCN3 protein
        mouse Hcn4 protein
        rat Hcn1 protein
        rat Hcn2 protein
        rat HCN3 protein
        rat HCN4 protein
  - Membrane Proteins: 10078
    - Membrane Glycoproteins: 2252
      - Ion Channels: 6731
        Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: 96
        human HCN1 protein
        human HCN2 protein
        human HCN3 protein
        human HCN4 protein
        mouse Hcn1 protein
        mouse Hcn2 protein
        mouse HCN3 protein
        mouse Hcn4 protein
        rat Hcn1 protein
        rat Hcn2 protein
        rat HCN3 protein
        rat HCN4 protein
    - Membrane Transport Proteins: 589
      - Ion Channels: 6731
        Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: 96
        human HCN1 protein
        human HCN2 protein
        human HCN3 protein
        human HCN4 protein
        mouse Hcn1 protein
        mouse Hcn2 protein
        mouse HCN3 protein
        mouse Hcn4 protein
        rat Hcn1 protein
        rat Hcn2 protein
        rat HCN3 protein
        rat HCN4 protein

Experts

1.	DiFrancesco, Dario: 6 articles (01/2019 - 08/2005)
2.	Ludwig, Andreas: 4 articles (01/2020 - 01/2003)
3.	Biel, Martin: 4 articles (10/2017 - 01/2003)
4.	Budde, Thomas: 3 articles (10/2022 - 01/2003)
5.	Petrou, Steven: 3 articles (01/2020 - 01/2012)
6.	Phillips, A Marie: 3 articles (01/2020 - 01/2012)
7.	Reid, Christopher A: 3 articles (01/2020 - 01/2012)
8.	Barbuti, Andrea: 3 articles (01/2019 - 11/2011)
9.	Milanesi, Raffaella: 3 articles (01/2019 - 11/2011)
10.	Fenske, Stefanie: 3 articles (10/2017 - 12/2013)

Related Diseases

1.	Pain (Aches) 05/15/2013 - "Blockers of voltage-gated Na(+) channels, openers of voltage-gated K(+) channels and blockers of hyperpolarization-activated cyclic nucleotide-gated channels that were found to reduce neuronal activity were also found to be effective in neuropathic and inflammatory pain states. " 09/07/2023 - "In this study, we used ex vivo whole-cell patch-clamp recording, immunofluorescence staining, and behavioral tests to examine whether hyperpolarization-activated cyclic nucleotide-gated channels 2 (HCN2) in the ventral hippocampal CA1 (vCA1) were involved in regulating nociceptive perception and CFA-induced inflammatory pain in mice. " 01/01/2017 - "Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) in the nervous system are implicated in a variety of neuronal functions including learning and memory, regulation of vigilance states and pain. " 08/01/2015 - "Hyperpolarization-activated cation channel-induced Ih current plays an important role in neuronal excitability and pathological pain. " 01/01/2009 - "HCN pacemaker channels and pain: a drug discovery perspective."
2.	Seizures (Absence Seizure) 10/05/2011 - "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. " 04/14/2006 - "We therefore reason that juvenile audiogenic seizures in Black Swiss mice are unlikely to be due to abnormalities of HCN2 channel function." 01/01/2016 - "Aberrant SUMOylation has been linked to neurological diseases that also display alterations in HCN1 and HCN2 channel expression, such as seizures and Parkinson's disease. " 10/03/2012 - "Hyperpolarization-activated cyclic nucleotide gated channels: a potential molecular link between epileptic seizures and Aβ generation in Alzheimer's disease." 01/01/2020 - "Importantly, EC18 was not protective against proconvulsant-mediated seizures in the conditional HCN4 channel knockout mouse and did not reduce bursting behaviour in AAV-HCN4 shRNA infected mouse cortical cultures. "
3.	Alcoholism (Alcohol Abuse) 04/01/2009 - "The results suggest that dopamine neuron I(H) channels, firing rate, and GABAergic input may play a role in sensitivity to the locomotor activation observed at early time points after ethanol administration and could underlie differences in sensitivity to alcohol relevant to risk for alcohol abuse." 01/01/2021 - "Bath application of Rp-cAMPs, a selective cAMP-PKA inhibitor, attenuated ACD-induced potentiation of EPSCs and IACD Finally, bath application of ZD7288, a selective blocker of hyperpolarization-activated cyclic nucleotide-gated channels, attenuated ACD-induced potentiation of firing, EPSCs, and IACD These results show that ACD exerts its aversive property by exciting LHb neurons via multiple cellular mechanisms, and new treatments targeting the LHb may be beneficial for alcoholism.SIGNIFICANCE STATEMENT Acetaldehyde (ACD) has been considered aversive peripherally and rewarding centrally. "
4.	Demyelinating Diseases (Demyelinating Disease) 10/08/2022 - "In addition, generalized demyelination resulted in a significant reduction in the amplitude of the hyperpolarization-activated inward current (Ih) in thalamic relay cells, which was accompanied by lower surface expression of hyperpolarization-activated, cyclic nucleotide-gated channels, and the phosphorylated form of TRIP8b (pS237-TRIP8b). "
5.	Neuralgia (Stump Neuralgia) 01/01/2019 - "In conclusion, the present study suggests that decreased HCN2 channel expression attenuates neuropathic pain by inhibiting pro-inflammatory reactions and NF-κB activation." 01/01/2019 - "Decreased HCN2 channel expression attenuates neuropathic pain by inhibiting pro-inflammatory reactions and NF-κB activation in mice." 04/08/2017 - "To explore the effects of hyperpolarization-activated cyclic nucleotide-gated channels 2(HCN2) in the formation of peripheral neuropathic pain in rats. " 06/25/2014 - "These results suggest that the CSF-contacting nucleus may be involved in the process of neuropathic pain via the HCN2 channel. " 06/25/2014 - "The purpose of this research is to explore the distribution and expression of hyperpolarization-activated cyclic nucleotide-gated channels subtype 2 (HCN2) in cerebrospinal fluid (CSF)-contacting nucleus in neuropathic pain, and provide experimental evidence to reveal the biological function and regulation mechanisms of CSF-contacting nucleus in neuropathic pain. "

Related Drugs and Biologics

1.	ICI D2788
2.	Small Interfering RNA (siRNA)
3.	Acetaldehyde
4.	adenosine-3',5'-cyclic phosphorothioate
5.	protein kinase modulator
6.	Proteins (Proteins, Gene)
7.	Ion Channels (Ion Channel)
8.	Brain-Derived Neurotrophic Factor (BDNF)
9.	Adenosine Monophosphate (AMP)
10.	Messenger RNA (mRNA)

Related Therapies and Procedures

1.	Nerve Block (Nerve Blocks)
2.	Electroacupuncture
3.	Therapeutics
4.	Pulsed Radiofrequency Treatment
5.	Axotomy