Evidence map›Paper›PMID 21518834›Full record

ArticleThe Journal of general physiology2011

Mode shift of the voltage sensors in Shaker K+ channels is caused by energetic coupling to the pore domain.

Georges A Haddad, Rikard Blunck

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of general physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

62 citing papers in PubMed, 79 citations in OpenAlex.

  1. Article
  2. Molecular Determinants of Voltage-Dependent Gating in Kv11.1 Channels.Advances in experimental medicine and biology · 2026
    Review
  3. A Historical Outline of Fluorescence Spectroscopy in Ion Channel Research.Advances in experimental medicine and biology · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. KCNG4 Genetic Variant Linked to Migraine Prevents Expression of KCNB1.International journal of molecular sciences · 2024
    Article
  8. Article
  9. Fifty years of gating currents and channel gating.The Journal of general physiology · 2023
    Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Modulation of hERG KFrontiers in pharmacology · 2020
    Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. S4-S5 linker movement during activation and inactivation in voltage-gated KProceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  20. Kv4.2 autism and epilepsy mutation enhances inactivation of closed channels but impairs access to inactivated state after opening.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article

2 more citing papers are in PubMed but not listed here.

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

2 authors at 1 institution in 2 countries.

Georges A HaddadGroupe d'étude des protéines membranaires, Département de physique, Université de Montréal, Montréal, Québec H3C 3J7, Canada.
Rikard Blunck
Laboratoire de Biologie Physico-Chimique des Protéines Membranaires · FR

Funding

Canadian Institutes of Health Research MOP-102689
6 · The paper itself

Abstract

The voltage sensors of voltage-gated ion channels undergo a conformational change upon depolarization of the membrane that leads to pore opening. This conformational change can be measured as gating currents and is thought to be transferred to the pore domain via an annealing of the covalent link between voltage sensor and pore (S4-S5 linker) and the C terminus of the pore domain (S6). Upon prolonged depolarizations, the voltage dependence of the charge movement shifts to more hyperpolarized potentials. This mode shift had been linked to C-type inactivation but has recently been suggested to be caused by a relaxation of the voltage sensor itself. In this study, we identified two ShakerIR mutations in the S4-S5 linker (I384N) and S6 (F484G) that, when mutated, completely uncouple voltage sensor movement from pore opening. Using these mutants, we show that the pore transfers energy onto the voltage sensor and that uncoupling the pore from the voltage sensor leads the voltage sensors to be activated at more negative potentials. This uncoupling also eliminates the mode shift occurring during prolonged depolarizations, indicating that the pore influences entry into the mode shift. Using voltage-clamp fluorometry, we identified that the slow conformational change of the S4 previously correlated with the mode shift disappears when uncoupling the pore. The effects can be explained by a mechanical load that is imposed upon the voltage sensors by the pore domain and allosterically modulates its conformation. Mode shift is caused by the stabilization of the open state but leads to a conformational change in the voltage sensor.

Indexed as

AnimalsIon Channel GatingMembrane PotentialsModels, MolecularMutagenesis, Site-DirectedOocytesPoint MutationProtein Structure, TertiaryShaker Superfamily of Potassium ChannelsXenopus laevisShaker Superfamily of Potassium Channels

Identifiers

PMID21518834
PMCPMC3082931
OpenAlexW2122429955

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.