ArticleScientific reports2015
Isoform dependent regulation of human HCN channels by cholesterol.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Sequential membrane remodeling by cholesterol distinctly modulates HCN channels in naïve and neuropathic DRG neurons.The Journal of general physiology · 2026Article
- Cannabidiol potentiates hyperpolarization-activated cyclic nucleotide-gated (HCN4) channels.The Journal of general physiology · 2024Article
- cAMP binding to closed pacemaker ion channels is cooperative.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Direct regulation of the voltage sensor of HCN channels by membrane lipid compartmentalization.Nature communications · 2023Article
- Modulating Hyperpolarization-Activated Cation Currents through Small Molecule Perturbations: Magnitude and Gating Control.Biomedicines · 2023Review
- Concerted suppressive effects of carisbamate, an anti-epileptic alkyl-carbamate drug, on voltage-gated NaFrontiers in cellular neuroscience · 2023Article
- Effective Perturbations by Small-Molecule Modulators on Voltage-Dependent Hysteresis of Transmembrane Ionic Currents.International journal of molecular sciences · 2022Review
- Characterization of Inhibitory Capability on Hyperpolarization-Activated Cation Current Caused by Lutein (β,ε-Carotene-3,3'-Diol), a Dietary Xanthophyll Carotenoid.International journal of molecular sciences · 2022Article
- Evidence for Dual Activation ofInternational journal of molecular sciences · 2022Article
- Alternative Targets for Modulators of Mitochondrial Potassium Channels.Molecules (Basel, Switzerland) · 2022Review
- Direct Regulation of Hyperpolarization-Activated Cyclic-Nucleotide Gated (HCN1) Channels by Cannabinoids.Frontiers in molecular neuroscience · 2022Article
- Computational Prediction of Phosphoinositide Binding to Hyperpolarization-Activated Cyclic-Nucleotide Gated Channels.Frontiers in physiology · 2022Article
- Review: HCN Channels in the Heart.Current cardiology reviews · 2022Review
- Article
- Effectiveness in Block by Dexmedetomidine of Hyperpolarization-Activated Cation Current, Independent of Its Agonistic Effect on αInternational journal of molecular sciences · 2020Article
- Effectiveness in the Block by Honokiol, a Dimerized Allylphenol fromInternational journal of molecular sciences · 2020Article
- Characterization of Convergent Suppression by UCL-2077 (3-(Triphenylmethylaminomethyl)pyridine), Known to Inhibit Slow Afterhyperpolarization, ofInternational journal of molecular sciences · 2020Article
- Characterization of Inhibitory Effectiveness in Hyperpolarization-Activated Cation Currents by a Group ofInternational journal of molecular sciences · 2020Article
- Characterization in Dual Activation by Oxaliplatin, a Platinum-Based Chemotherapeutic Agent of Hyperpolarization-Activated Cation and Electroporation-Induced Currents.International journal of molecular sciences · 2020Article
- Characterization of Effectiveness in ConcertedInternational journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholesterol has been shown to regulate numerous ion channels. HCN channels represent the molecular correlate of If or Ih in sinoatrial node (SAN) and neuronal cells. Previous studies have implicated a role for cholesterol in the regulation of rabbit HCN4 channels with effects on pacing in the rabbit SAN. Using electrophysiological and biochemical approaches, we examined the effect of cholesterol modulation on human HCN1, HCN2 and HCN4 isoforms. Patch-clamp experiments uncovered isoform specific differences in the effect of cholesterol on gating kinetics upon depletion by MβCD or mevastatin or enrichment using MβCD/cholesterol. Most dramatically cholesterol had isoform specific effects on mode-shifting, which has been suggested to play a key role in stabilizing firing rate and preventing arrhythmic firing in SAN cells and neurons. Mode-shifting in HCN1 channels was insensitive to cholesterol manipulation, while HCN2 and HCN4 were strongly affected. Trafficking of each isoform to the plasma membrane was also affected by cholesterol modulation differentially between isoforms, however, each isoform remained localized in lipid raft domains after cholesterol depletion. These effects may contribute to the side effects of cholesterol reducing therapies including disrupted heart rhythm and neuropathic pain, as well as the susceptibility of sinus dysfunction in patients with elevated cholesterol.
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