ArticleProceedings of the National Academy of Sciences of the United States of America2024
cAMP binding to closed pacemaker ion channels is cooperative.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 7 citations in OpenAlex.
- Lipid bilayers determine allostery but not intrinsic affinity of cAMP to pacemaker channels.Nature communications · 2026Article
- Ligand Binding Dynamics of Ion Channels and GPCRs Using Single-Molecule Fluorescence.Annual review of biophysics · 2026Review
- An inter-subunit path is required for entropically-driven and negatively cooperative binding of cyclic nucleotides in the HCN2 channel.Communications biology · 2026Article
- Membrane-forming phospholipids allosterically modulate native-state prolyl isomerization in a CNG channel.Protein science : a publication of the Protein Society · 2025Article
- Using Bayesian priors to overcome non-identifiablility issues in Hidden Markov models.bioRxiv : the preprint server for biology · 2025Article
- Comparative Analysis of Volatile Components in Chi-Nan and Ordinary Agarwood Aromatherapies: Implications for Sleep Improvement.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Anisotropic Network Analysis of Open/Closed HCN4 Channel Advocates Asymmetric Subunit Cooperativity in cAMP Modulation of Gating.Journal of chemical information and modeling · 2024Article
- Similar Binding Modes of cGMP Analogues Limit Selectivity in Modulating Retinal CNG Channels via the Cyclic Nucleotide-Binding Domain.ACS chemical neuroscience · 2024Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The cooperative action of the subunits in oligomeric receptors enables fine-tuning of receptor activation, as demonstrated for the regulation of voltage-activated HCN pacemaker ion channels by relating cAMP binding to channel activation in ensemble signals. HCN channels generate electric rhythmicity in specialized brain neurons and cardiomyocytes. There is conflicting evidence on whether binding cooperativity does exist independent of channel activation or not, as recently reported for detergent-solubilized receptors positioned in zero-mode waveguides. Here, we show positive cooperativity in ligand binding to closed HCN2 channels in native cell membranes by following the binding of individual fluorescence-labeled cAMP molecules. Kinetic modeling reveals that the affinity of the still empty binding sites rises with increased degree of occupation and that the transition of the channel to a flip state is promoted accordingly. We conclude that ligand binding to the subunits in closed HCN2 channels not pre-activated by voltage is already cooperative. Hence, cooperativity is not causally linked to channel activation by voltage. Our analysis also shows that single-molecule binding measurements at equilibrium can quantify cooperativity in ligand binding to receptors in native membranes.
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Registered trials
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.