Evidence map›Paper›PMID 19578067›Full record

ArticleCardiovascular research2009

Dissociation of FKBP12.6 from ryanodine receptor type 2 is regulated by cyclic ADP-ribose but not beta-adrenergic stimulation in mouse cardiomyocytes.

Xu Zhang, Yvonne N Tallini, Zheng Chen, Lu Gan, Bin Wei, Robert Doran, Lin Miao, Hong-Bo Xin, Michael I Kotlikoff, Guangju Ji

Open access · bronzeAbstract read
In one paragraph

Article in Cardiovascular research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.9field-weighted citation impact, top 7% 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

22 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Review
  3. The Impact of Intermittent Hypoxia on Metabolism and Cognition.International journal of molecular sciences · 2022
    Review
  4. Article
  5. Article
  6. Roles of NADMolecules (Basel, Switzerland) · 2020
    Review
  7. Calcium Signaling in Cardiomyocyte Function.Cold Spring Harbor perspectives in biology · 2020
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Cyclic ADP-Ribose and NAADP in Vascular Regulation and Diseases.Messenger (Los Angeles, Calif. : Print) · 2013
    Article
  18. Article
  19. Selective inhibitors of cardiac ADPR cyclase as novel anti-arrhythmic compounds.Naunyn-Schmiedeberg's archives of pharmacology · 2012
    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

10 authors at 5 institutions in 2 countries.

Xu ZhangNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
Yvonne N Tallini
Zheng Chen
Lu Gan
Bin Wei
Robert Doran
Lin Miao
Hong-Bo Xin
Michael I Kotlikoff
Guangju Ji
Institute of Biophysics · CNNew York State College of Veterinary Medicine · USSichuan University · CNChinese Academy of Sciences · CNCornell University · US

Funding

Smooth Muscle Ca Release in RYR and FKBP transgenic miceR01HL045239 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI KOTLIKOFF, MICHAEL I. · 1990 to 2006
$2.2M
Transgenic Mice- Recomb., Fate-Mapping,and Ca2+signalingR01DK065992 · NIDDK · CORNELL UNIVERSITY ITHACA · PI KOTLIKOFF, MICHAEL I. · 2004 to 2008
$1.9M
NHLBI NIH HHS HL45239NIDDK NIH HHS DK65992
6 · The paper itself

Abstract

aimsBeta-adrenergic augmentation of Ca(2+) sparks and cardiac contractility has been functionally linked to phosphorylation-dependent dissociation of FK506 binding protein 12.6 (FKBP12.6) regulatory proteins from ryanodine receptors subtype 2 (RYR2). We used FKBP12.6 null mice to test the extent to which the dissociation of FKBP12.6 affects Ca(2+) sparks and mediates the inotropic action of isoproterenol (ISO), and to investigate the underlying mechanisms of cyclic ADP-ribose (cADPR) regulation of Ca(2+) sparks. METHODS AND

resultsCa(2+) sparks and contractility were measured in cardiomyocytes and papillary muscle segments from FKBP12.6 null mice, and western blot analysis was carried out on sarcoplasmic reticulum microsomes prepared from mouse heart. Exposure to ISO resulted in a three- and two-fold increase in Ca(2+) spark frequency in wild-type (WT) and FKBP12.6 knockout (KO) myocytes, respectively, and Ca(2+) spark kinetics were also significantly altered in both types of cells. The effects of ISO on Ca(2+) spark properties in KO cells were inhibited by pre-treatment with thapsigargin or phospholamban inhibitory antibody, 2D12. Moreover, twitch force magnitude and the rate of force development were not significantly different in papillary muscles from WT and KO mice. Unlike beta-adrenergic stimulation, cADPR stimulation increased Ca(2+) spark frequency (2.8-fold) and altered spark kinetics only in WT but not in KO mice. The effect of cADPR on spark properties was not entirely blocked by pre-treatment with thapsigargin or 2D12. In voltage-clamped cells, cADPR increased the peak Ca(2+) of the spark without altering the decay time. We also noticed that basal Ca(2+) spark properties in KO mice were markedly altered compared with those in WT mice.

conclusionOur data demonstrate that dissociation of FKBP12.6 from the RYR2 complex does not play a significant role in beta-adrenergic-stimulated Ca(2+) release in heart cells, whereas this mechanism does underlie the action of cADPR.

Indexed as

Action PotentialsAdrenergic beta-AgonistsAnimalsCalcium-Binding ProteinsCalcium SignalingCyclic ADP-RiboseCyclic AMP-Dependent Protein KinasesEnzyme InhibitorsFemaleIsoproterenolKineticsMaleMiceMice, KnockoutMyocardial ContractionMyocytes, CardiacAdrenergic beta-AgonistsCalcium-Binding ProteinsCyclic ADP-RiboseCyclic AMP-Dependent Protein KinasesEnzyme InhibitorsFKBP1B protein, mouseIsoproterenolPhospholambanReceptors, Adrenergic, betaRyanodine Receptor Calcium Release ChannelSarcoplasmic Reticulum Calcium-Transporting ATPasesTacrolimus Binding ProteinsThapsigargin

Identifiers

PMID19578067
PMCPMC2761199
OpenAlexW2096624868

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.