ArticleThe Journal of general physiology2018
Minimal molecular determinants of isoform-specific differences in efficacy in the HCN channel family.
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 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Structure mirroring function: What's the 'matter' with the funny current?The Journal of physiology · 2026Review
- HCN1 is a primary HCN Pacemaker Channel in Neurons.Nature communications · 2026Article
- Predicting Binding Affinities for the Binding Domain of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Isoforms Using Free-Energy Perturbation.bioRxiv : the preprint server for biology · 2026Article
- Towards a unified gating scheme for the CNBD ion channel family.The Journal of general physiology · 2026Review
- 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
- Activation of CB1R alleviates central sensitization by regulating HCN2-pNR2B signaling in a chronic migraine rat model.The journal of headache and pain · 2023Article
- Blockage of HCN Channels Inhibits the Function of P2X Receptors in Rat Dorsal Root Ganglion Neurons.Neurochemical research · 2022Article
- Two HCN4 Channels Play Functional Roles in the Zebrafish Heart.Frontiers in physiology · 2022Article
- Er81 Transcription Factor Fine-Tunes Striatal Cholinergic Interneuron Activity and Drives Habit Formation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Allosteric signaling in C-linker and cyclic nucleotide-binding domain of HCN2 channels.Biophysical journal · 2021Article
- Article
- Constitutively active HCN channels constrain detrusor excitability and modulate evoked contractions of human bladder.American journal of clinical and experimental urology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels generate rhythmic activity in the heart and brain. Isoform-specific functional differences reflect the specializations required for the various roles that they play. Despite a high sequence and structural similarity, HCN isoforms differ greatly in their response to cyclic nucleotides. Cyclic AMP (cAMP) enhances the activity of HCN2 and HCN4 isoforms by shifting the voltage dependence of activation to more depolarized potentials, whereas HCN1 and HCN3 isoforms are practically insensitive to this ligand. Here, to determine the molecular basis for increased cAMP efficacy in HCN2 channels, we progressively mutate residues in the C-linker and cyclic nucleotide-binding domain (CNBD) of the mouse HCN2 to their equivalents in HCN1. We identify two clusters of mutations that determine the differences in voltage-dependent activation between these two isoforms. One maps to the C-linker region, whereas the other is in proximity to the cAMP-binding site in the CNBD. A mutant channel containing just five mutations (M485I, G497D, S514T, V562A, and S563G) switches cAMP sensitivity of full-length HCN2 to that of HCN1 channels. These findings, combined with a detailed analysis of various allosteric models for voltage- and ligand-dependent gating, indicate that these residues alter the ability of the C-linker to transduce signals from the CNBD to the pore gates of the HCN channel.
Indexed as
Identifiers
What OpenQuestion holds
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.