Evidence map›Paper›PMID 22556415›Full record

ArticleThe Journal of biological chemistry2012

The contribution of RCK domains to human BK channel allosteric activation.

Nicoletta Savalli, Antonios Pantazis, Taleh Yusifov, Daniel Sigg, Riccardo Olcese

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Fifty years of gating currents and channel gating.The Journal of general physiology · 2023
    Review
  6. Article
  7. Article
  8. Regulatory mechanisms of mitochondrial BKChannels (Austin, Tex.) · 2021
    Review
  9. Review
  10. Coupling of CaProceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  11. Article
  12. Article
  13. Article
  14. Physiological Roles and Therapeutic Potential of CaFrontiers in molecular neuroscience · 2018
    Review
  15. Review
  16. Large-conductance CaThe Journal of physiology · 2017
    Article
  17. Understanding the conformational motions of RCK gating rings.The Journal of general physiology · 2017
    Review
  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

5 authors.

Nicoletta SavalliDepartment of Anesthesiology, Division of Molecular Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90075, USA.
Antonios Pantazis
Taleh Yusifov
Daniel Sigg
Riccardo Olcese

Funding

Structural Changes in BKCa Channels During GatingR01GM082289 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI OLCESE, RICCARDO · 2008 to 2011
$1.4M
NIGMS NIH HHS R01 GM082289NIGMS NIH HHS R01GM082289
6 · The paper itself

Abstract

Large conductance voltage- and Ca(2+)-activated K(+) (BK) channels are potent regulators of cellular processes including neuronal firing, synaptic transmission, cochlear hair cell tuning, insulin release, and smooth muscle tone. Their unique activation pathway relies on structurally distinct regulatory domains including one transmembrane voltage-sensing domain (VSD) and two intracellular high affinity Ca(2+)-sensing sites per subunit (located in the RCK1 and RCK2 domains). Four pairs of RCK1 and RCK2 domains form a Ca(2+)-sensing apparatus known as the "gating ring." The allosteric interplay between voltage- and Ca(2+)-sensing apparati is a fundamental mechanism of BK channel function. Using voltage-clamp fluorometry and UV photolysis of intracellular caged Ca(2+), we optically resolved VSD activation prompted by Ca(2+) binding to the gating ring. The sudden increase of intracellular Ca(2+) concentration ([Ca(2+)](i)) induced a hyperpolarizing shift in the voltage dependence of both channel opening and VSD activation, reported by a fluorophore labeling position 202, located in the upper side of the S4 transmembrane segment. The neutralization of the Ca(2+) sensor located in the RCK2 domain abolished the effect of [Ca(2+)](i) increase on the VSD rearrangements. On the other hand, the mutation of RCK1 residues involved in Ca(2+) sensing did not prevent the effect of Ca(2+) release on the VSD, revealing a functionally distinct interaction between RCK1 and RCK2 and the VSD. A statistical-mechanical model quantifies the complex thermodynamics interplay between Ca(2+) association in two distinct sites, voltage sensor activation, and BK channel opening.

Indexed as

Allosteric SiteBinding SitesCalciumCalcium ChannelsElectrophysiologyFluorometryHumansIon Channel GatingLarge-Conductance Calcium-Activated Potassium ChannelsMembrane PotentialsModels, MolecularMolecular ConformationPhotolysisProtein BindingThermodynamicsUltraviolet RaysCalciumCalcium ChannelsLarge-Conductance Calcium-Activated Potassium Channels

Identifiers

PMID22556415
PMCPMC3381136

What OpenQuestion holds

Textmetadata
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.