ArticleThe Journal of general physiology2018
All four subunits of HCN2 channels contribute to the activation gating in an additive but intricate manner.
Article in The Journal of general physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- The proximal N-terminus of IRAG is required for potentiation of HCN4 channels.bioRxiv : the preprint server for biology · 2026Article
- An inter-subunit path is required for entropically-driven and negatively cooperative binding of cyclic nucleotides in the HCN2 channel.Communications biology · 2026Article
- Subunit-specific conductance of single homomeric and heteromeric HCN pacemaker channels at femtosiemens resolution.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Anisotropic Network Analysis of Open/Closed HCN4 Channel Advocates Asymmetric Subunit Cooperativity in cAMP Modulation of Gating.Journal of chemical information and modeling · 2024Article
- LRMP inhibits cAMP potentiation of HCN4 channels by disrupting intramolecular signal transduction.eLife · 2024Article
- cAMP binding to closed pacemaker ion channels is cooperative.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- LRMP inhibits cAMP potentiation of HCN4 channels by disrupting intramolecular signal transduction.bioRxiv : the preprint server for biology · 2024Article
- Identifiability of equilibrium constants for receptors with two to five binding sites.The Journal of general physiology · 2023Article
- Functional and structural characterization of interactions between opposite subunits in HCN pacemaker channels.Communications biology · 2022Article
- Uncoupling of Voltage- and Ligand-Induced Activation in HCN2 Channels by Glycine Inserts.Frontiers in physiology · 2022Article
- Thermodynamic profile of mutual subunit control in a heteromeric receptor.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Loss of HCN2 in Dorsal Hippocampus of Young Adult Mice Induces Specific Apoptosis of the CA1 Pyramidal Neuron Layer.International journal of molecular sciences · 2021Article
- Allosteric signaling in C-linker and cyclic nucleotide-binding domain of HCN2 channels.Biophysical journal · 2021Article
- HCN Channels: New Therapeutic Targets for Pain Treatment.Molecules (Basel, Switzerland) · 2018Review
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5 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are tetramers that elicit electrical rhythmicity in specialized brain neurons and cardiomyocytes. The channels are dually activated by voltage and binding of cyclic adenosine monophosphate (cAMP) to their four cyclic nucleotide-binding domains (CNBDs). Here we analyze the effects of cAMP binding to different concatemers of HCN2 channel subunits, each having a defined number of functional CNBDs. We show that each liganded CNBD promotes channel activation in an additive manner and that, in the special case of two functional CNBDs, functionality does not depend on the arrangement of the subunits. Correspondingly, the reverse process of deactivation is slowed by progressive liganding, but only if four and three ligands as well as two ligands in trans position (opposite to each other) are bound. In contrast, two ligands bound in cis positions (adjacent to each other) and a single bound ligand do not affect channel deactivation. These results support an activation mechanism in which each single liganded CNBD causes a turning momentum on the tetrameric ring-like structure formed by all four CNBDs and that at least two liganded subunits in trans positions are required to maintain activation.
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