Evidence map›Paper›PMID 41326336›Full record

ArticleNature communications2025

Extracellular activation of HCN4 by a subtype-specific nanobody.

Atiyeh Sadat Sharifzadeh, Roberta Castelli, Alessandro Porro, Pietro Mesirca, Romain Perrier, Ana M Gómez, Nadia Mekrane, Hugo Benoit, Albano C Meli, Luca M G Palloni and 5 more

Abstract read
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In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Atiyeh Sadat Sharifzadeh *Department of Biosciences, University of Milan, Milan, Italy.
Roberta Castelli *Department of Biosciences, University of Milan, Milan, Italy.ORCID http://orcid.org/0009-0000-6773-7486
Alessandro PorroDepartment of Biosciences, University of Milan, Milan, Italy.ORCID http://orcid.org/0000-0003-4845-6165
Pietro MesircaInstitut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, France.ORCID http://orcid.org/0000-0002-9538-3096
Romain PerrierSignaling and Cardiovascular Pathophysiology, Université Paris-Saclay, INSERM UMR-S 1180, Orsay, France.ORCID http://orcid.org/0000-0003-2229-4700
Ana M GómezSignaling and Cardiovascular Pathophysiology, Université Paris-Saclay, INSERM UMR-S 1180, Orsay, France.ORCID http://orcid.org/0000-0003-0009-2884
Nadia MekraneInstitut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, France.
Hugo BenoitPhyMedExp, University of Montpellier, CNRS, INSERM, Montpellier, France.
Albano C MeliPhyMedExp, University of Montpellier, CNRS, INSERM, Montpellier, France.
Luca M G PalloniDepartment of Biosciences, University of Milan, Milan, Italy.
Dario DiFrancescoDepartment of Biosciences, University of Milan, Milan, Italy.ORCID http://orcid.org/0000-0002-7322-1790
Matteo E MangoniInstitut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, France.ORCID http://orcid.org/0000-0002-8892-3373
Gerhard ThielDepartment of Biosciences, University of Milan, Milan, Italy.
Andrea SaponaroDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. andrea.saponaro@unimi.it.ORCID http://orcid.org/0000-0001-5035-5174
Anna MoroniDepartment of Biosciences, University of Milan, Milan, Italy. anna.moroni@unimi.it.ORCID http://orcid.org/0000-0002-1860-406X

Funding

EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) 101118744Fondazione Telethon (Telethon Foundation) GGP20021
6 · The paper itself

Abstract

Hyperpolarization-activated cyclic nucleotide-gated channels (HCN1-4) control cardiac and neuronal firing and their dysfunction leads to cardiac arrythmias (HCN4), epilepsy (HCN1) and chronic pain (HCN2). Prompted by the urgent need for HCN subtype-specific treatments, we screened a recombinant nanobody library in search of HCN4-specific binders. Here we show that nanobody 5 (NB5) binds to the extracellular side of HCN4 with high specificity and nanomolar affinity and activates the channel by a non-canonical electromechanical coupling path. In ex vivo and in vitro experiments, NB5 acts as an agonist of the pacemaker current I

Indexed as

Hyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMuscle ProteinsPotassium ChannelsSingle-Domain AntibodiesAnimalsBradycardiaHEK293 CellsHumansMutationMyocytes, CardiacRabbitsHCN4 protein, humanHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMuscle ProteinsPotassium ChannelsSingle-Domain Antibodies

Identifiers

PMID41326336
PMCPMC12669647

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.