Evidence map›Paper›PMID 21746845›Full record

ArticleThe Journal of general physiology2011

Spatial organization of RYRs and BK channels underlying the activation of STOCs by Ca(2+) sparks in airway myocytes.

Lawrence M Lifshitz, Jeffrey D Carmichael, F Anthony Lai, Vincenzo Sorrentino, Karl Bellvé, Kevin E Fogarty, Ronghua ZhuGe

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 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

25 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. CaPhysiological reviews · 2024
    Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. BKAntioxidants (Basel, Switzerland) · 2020
    Review
  9. Article
  10. CaThe Journal of physiology · 2019
    Article
  11. Article
  12. Article
  13. Pregnancy Increases CaHypertension (Dallas, Tex. : 1979) · 2019
    Article
  14. The augmentation of BK channel activity by nitric oxide signaling in rat cerebral arteries involves co-localized regulatory elements.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017
    Article
  15. Article
  16. Article
  17. Article
  18. Modulating Ca²⁺ signals: a common theme for TMEM16, Ist2, and TMC.Pflugers Archiv : European journal of physiology · 2016
    Review
  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

7 authors at 4 institutions in 4 countries.

Lawrence M LifshitzBiomedical Imaging Group, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Jeffrey D Carmichael
F Anthony Lai
Vincenzo Sorrentino
Karl Bellvé
Kevin E Fogarty
Ronghua ZhuGe
Laboratoire d’Imagerie Biomédicale · FRCardiff University · GBUniversity of Massachusetts Chan Medical School · USUniversity of Siena · IT

Funding

Ca2+ Sparks as Regulators of Airway ContractilityR01HL073875 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ZHUGE, RONGHUA · 2004 to 2007
$1.3M
British Heart Foundation GGP08153NHLBI NIH HHS HL73875NHLBI NIH HHS R01 HL073875Telethon GGP08153
6 · The paper itself

Abstract

Short-lived, localized Ca(2+) events mediate Ca(2+) signaling with high efficiency and great fidelity largely as a result of the close proximity between Ca(2+)-permeable ion channels and their molecular targets. However, in most cases, direct evidence of the spatial relationship between these two types of molecules is lacking, and, thus, mechanistic understanding of local Ca(2+) signaling is incomplete. In this study, we use an integrated approach to tackling this issue on a prototypical local Ca(2+) signaling system composed of Ca(2+) sparks resulting from the opening of ryanodine receptors (RYRs) and spontaneous transient outward currents (STOCs) caused by the opening of Ca(2+)-activated K(+) (BK) channels in airway smooth muscle. Biophysical analyses of STOCs and Ca(2+) sparks acquired at 333 Hz demonstrate that these two events are associated closely in time, and approximately eight RYRs open to give rise to a Ca(2+) spark, which activates ∼15 BK channels to generate a STOC at 0 mV. Dual immunocytochemistry and 3-D deconvolution at high spatial resolution reveal that both RYRs and BK channels form clusters and RYR1 and RYR2 (but not RYR3) localize near the membrane. Using the spatial relationship between RYRs and BK channels, the spatial-temporal profile of [Ca(2+)] resulting from Ca(2+) sparks, and the kinetic model of BK channels, we estimate that an average Ca(2+) spark caused by the opening of a cluster of RYR1 or RYR2 acts on BK channels from two to three clusters that are randomly distributed within an ∼600-nm radius of RYRs. With this spatial organization of RYRs and BK channels, we are able to model BK channel currents with the same salient features as those observed in STOCs across a range of physiological membrane potentials. Thus, this study provides a mechanistic understanding of the activation of STOCs by Ca(2+) sparks using explicit knowledge of the spatial relationship between RYRs (the Ca(2+) source) and BK channels (the Ca(2+) target).

Indexed as

AnimalsCalciumCalcium SignalingIon ChannelsMaleMembrane PotentialsMiceModels, TheoreticalMuscle CellsMuscle, SmoothPatch-Clamp TechniquesPotassium Channels, Calcium-ActivatedProtein IsoformsRyanodine Receptor Calcium Release ChannelCalciumIon ChannelsPotassium Channels, Calcium-ActivatedProtein IsoformsRyanodine Receptor Calcium Release Channel

Identifiers

PMID21746845
PMCPMC3149436
OpenAlexW2130577747

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.