Evidence map›Paper›PMID 33990563›Full record

ArticleNature communications2021

Electromechanical coupling mechanism for activation and inactivation of an HCN channel.

Gucan Dai, Teresa K Aman, Frank DiMaio, William N Zagotta

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
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

20 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Extracellular salt bridge networks around S4 implicated in HCN channel gating and heart disease.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Article
  4. Article
  5. Deep Learning-Based Ion Channel Kinetics Analysis for Automated Patch Clamp Recording.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  6. Plants (Basel, Switzerland) · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Paradigm shift: new concepts for HCN4 function in cardiac pacemaking.Pflugers Archiv : European journal of physiology · 2022
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
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

4 authors at 1 institution in 1 country.

Gucan DaiDepartment of Physiology and Biophysics, University of Washington, Seattle, WA, USA. daig@uw.edu.ORCID 0000-0002-4692-4060
Teresa K AmanDepartment of Physiology and Biophysics, University of Washington, Seattle, WA, USA.
Frank DiMaioDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
William N ZagottaDepartment of Physiology and Biophysics, University of Washington, Seattle, WA, USA. zagotta@uw.edu.ORCID 0000-0002-7631-8168
University of Washington · US

Funding

GATING MECHANISMS OF RETINAL ROD CGMP-ACTIVATED CHANNELSR01EY010329 · NEI · UNIVERSITY OF WASHINGTON · PI ZAGOTTA, WILLIAM N · 1994 to 2023
$7.7M
Regulation of KCNH ion channelsR01MH102378 · NIMH · UNIVERSITY OF WASHINGTON · PI ZAGOTTA, WILLIAM N · 2014 to 2018
$1.9M
Supplement to Multimodal Gating Mechanisms of TRPV1 Ion ChannelsR01GM125351 · NIGMS · UNIVERSITY OF WASHINGTON · PI GORDON, SHARONA E · 2018 to 2021
$1.8M
Structural mechanisms for gating of bacterial cyclic nucleotide-gated ion channelsR01GM127325 · NIGMS · UNIVERSITY OF WASHINGTON · PI ZAGOTTA, WILLIAM N · 2018 to 2021
$1.6M
Protein kinase A modulation of NMDA receptor gating and permeabilityF32NS077622 · NINDS · UNIVERSITY OF WASHINGTON · PI AMAN, TERESA K · 2012 to 2014
$156k
NEI NIH HHS R01 EY010329NIGMS NIH HHS R01 GM125351NIGMS NIH HHS R01 GM127325NIMH NIH HHS R01 MH102378NINDS NIH HHS F32 NS077622
6 · The paper itself

Abstract

Pacemaker hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels exhibit a reversed voltage-dependent gating, activating by membrane hyperpolarization instead of depolarization. Sea urchin HCN (spHCN) channels also undergo inactivation with hyperpolarization which occurs only in the absence of cyclic nucleotide. Here we applied transition metal ion FRET, patch-clamp fluorometry and Rosetta modeling to measure differences in the structural rearrangements between activation and inactivation of spHCN channels. We found that removing cAMP produced a largely rigid-body rotation of the C-linker relative to the transmembrane domain, bringing the A' helix of the C-linker in close proximity to the voltage-sensing S4 helix. In addition, rotation of the C-linker was elicited by hyperpolarization in the absence but not the presence of cAMP. These results suggest that - in contrast to electromechanical coupling for channel activation - the A' helix serves to couple the S4-helix movement for channel inactivation, which is likely a conserved mechanism for CNBD-family channels.

Indexed as

AnimalsCyclic AMPCyclic Nucleotide-Gated Cation ChannelsFemaleFluorescence Resonance Energy TransferHumansHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsIon Channel GatingMaleMechanotransduction, CellularMembrane PotentialsModels, MolecularOocytesPatch-Clamp TechniquesProtein Conformation, alpha-HelicalProtein DomainsCyclic AMPCyclic Nucleotide-Gated Cation ChannelsHyperpolarization-Activated Cyclic Nucleotide-Gated Channels

Identifiers

PMID33990563
PMCPMC8121817
OpenAlexW3163577615

What OpenQuestion holds

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LicenceCC BY
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 OpenQuestion graph.