ArticleNature chemical biology2011
How subunits cooperate in cAMP-induced activation of homotetrameric HCN2 channels.
Article in Nature chemical biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 76 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
- Structure mirroring function: What's the 'matter' with the funny current?The Journal of physiology · 2026Review
- An inter-subunit path is required for entropically-driven and negatively cooperative binding of cyclic nucleotides in the HCN2 channel.Communications biology · 2026Article
- Anisotropic Network Analysis of Open/Closed HCN4 Channel Advocates Asymmetric Subunit Cooperativity in cAMP Modulation of Gating.Journal of chemical information and modeling · 2024Article
- cAMP binding to closed pacemaker ion channels is cooperative.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A high affinity switch for cAMP in the HCN pacemaker channels.Nature communications · 2024Article
- Fast functional mapping of ligand-gated ion channels.Communications biology · 2023Article
- Kinetic fingerprinting of metabotropic glutamate receptors.Communications biology · 2023Article
- Subunit promotion energies for channel opening in heterotetrameric olfactory CNG channels.PLoS computational biology · 2022Article
- Enlightening activation gating in P2X receptors.Purinergic signalling · 2022Review
- Article
- Altered cyclic nucleotide binding and pore opening in a diseased human HCN4 channel.Biophysical journal · 2022Article
- Validation of the binding stoichiometry between HCN channels and their neuronal regulator TRIP8b by single molecule measurements.Frontiers in physiology · 2022Article
- The Nature of Noradrenergic Volume Transmission From Locus Coeruleus to Brainstem Mesencephalic Trigeminal Sensory Neurons.Frontiers in cellular neuroscience · 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
- Article
- Optogenetic modulation of real-time nanoscale dynamics of HCN channels using photoactivated adenylyl cyclases.RSC chemical biology · 2021Article
- Allosteric signaling in C-linker and cyclic nucleotide-binding domain of HCN2 channels.Biophysical journal · 2021Article
- Unravelling the intricate cooperativity of subunit gating in P2X2 ion channels.Scientific reports · 2020Article
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are tetrameric membrane proteins that generate electrical rhythmicity in specialized neurons and cardiomyocytes. The channels are primarily activated by voltage but are receptors as well, binding the intracellular ligand cyclic AMP. The molecular mechanism of channel activation is still unknown. Here we analyze the complex activation mechanism of homotetrameric HCN2 channels by confocal patch-clamp fluorometry and kinetically quantify all ligand binding steps and closed-open isomerizations of the intermediate states. For the binding affinity of the second, third and fourth ligand, our results suggest pronounced cooperativity in the sequence positive, negative and positive, respectively. This complex interaction of the subunits leads to a preferential stabilization of states with zero, two or four ligands and suggests a dimeric organization of the activation process: within the dimers the cooperativity is positive, whereas it is negative between the dimers.
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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.