ArticleBritish journal of pharmacology2012
Novel blockers of hyperpolarization-activated current with isoform selectivity in recombinant cells and native tissue.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 52 citations in OpenAlex.
- Interleukin-6 Modulates the Expression and Function of HCN Channels: A Link Between Inflammation and Atrial Electrogenesis.International journal of molecular sciences · 2024Article
- An anchor-tether 'hindered' HCN1 inhibitor is antihyperalgesic in a rat spared nerve injury neuropathic pain model.British journal of anaesthesia · 2023Article
- Modulating Hyperpolarization-Activated Cation Currents through Small Molecule Perturbations: Magnitude and Gating Control.Biomedicines · 2023Review
- A Novel Flow Cytometry-Based Assay for the Identification of HCN4 CNBD Ligands.Pharmaceuticals (Basel, Switzerland) · 2023Article
- The Impact of Altered HCN1 Expression on Brain Function and Its Relationship with Epileptogenesis.Current neuropharmacology · 2023Review
- Seizures, behavioral deficits, and adverse drug responses in two new genetic mouse models ofeLife · 2022Article
- Review: HCN Channels in the Heart.Current cardiology reviews · 2022Review
- Effect of Ivabradine on Cardiac Ventricular Arrhythmias: Friend or Foe?Journal of clinical medicine · 2021Review
- Non-canonical Molecular Targets for Novel Analgesics: Intracellular Calcium and HCN Channels.Current neuropharmacology · 2021Review
- The hyperpolarization-activated cyclic nucleotide-gated 4 channel as a potential anti-seizure drug target.British journal of pharmacology · 2020Article
- Cardiac and neuronal HCN channelopathies.Pflugers Archiv : European journal of physiology · 2020Review
- Identification and characterization of a series of novel HCN channel inhibitors.Acta pharmacologica Sinica · 2019Article
- The Hyperpolarization-Activated HCN4 Channel is Important for Proper Maintenance of Oscillatory Activity in the Thalamocortical System.Cerebral cortex (New York, N.Y. : 1991) · 2019Article
- EC18 as a Tool To Understand the Role of HCN4 Channels in Mediating Hyperpolarization-Activated Current in Tissues.ACS medicinal chemistry letters · 2019Article
- Article
- Inhibition of hyperpolarization-activated cyclic nucleotide-gated channels by β-blocker carvedilol.British journal of pharmacology · 2018Article
- HCN Channels: New Therapeutic Targets for Pain Treatment.Molecules (Basel, Switzerland) · 2018Review
- Selective Blockade of HCN1/HCN2 Channels as a Potential Pharmacological Strategy Against Pain.Frontiers in pharmacology · 2018Article
- The Hyperpolarization-Activated Current Determines Synaptic Excitability, Calcium Activity and Specific Viability of Substantia Nigra Dopaminergic Neurons.Frontiers in cellular neuroscience · 2017Article
- Addictive neurons.Therapeutic targets for neurological diseases · 2017Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND PURPOSE Selective hyperpolarization activated, cyclic nucleotide-gated channel (HCN) blockers represent an important therapeutic goal due to the wide distribution and multiple functions of these proteins, representing the molecular correlate of f- and h-current (I(f) or I(h) ). Recently, new compounds able to block differentially the homomeric HCN isoforms expressed in HEK293 have been synthesized. In the present work, the electrophysiological and pharmacological properties of these new HCN blockers were characterized and their activities evaluated on native channels. EXPERIMENTAL APPROACH HEK293 cells expressing mHCN1, mHCN2 and hHCN4 isoforms were used to verify channel blockade. Selected compounds were tested on native guinea pig sinoatrial node cells and neurons from mouse dorsal root ganglion (DRG) by patch-clamp recordings and on dog Purkinje fibres by intracellular recordings. KEY RESULTS In HEK293 cells, EC18 was found to be significantly selective for HCN4 and MEL57A for HCN1 at physiological membrane potential. When tested on guinea pig sinoatrial node cells, EC18 (10 µM) maintained its activity, reducing I(f) by 67% at -120 mV, while MEL57A (3 µM) reduced I(f) by 18%. In contrast, in mouse DRG neurons, only MEL57A (30 and 100 µM) significantly reduced I(h) by 60% at -80 mV. In dog cardiac Purkinje fibres, EC18, but not MEL57A, reduced the amplitude and slowed the slope of the spontaneous diastolic depolarization. CONCLUSIONS Our results have identified novel and highly selective HCN isoform blockers, EC18 and MEL57A; the selectivity found in recombinant system was maintained in various tissues expressing different HCN isoforms.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.