ArticleThe Biochemical journal2003
In situ modulation of the human cardiac ryanodine receptor (hRyR2) by FKBP12.6.
Article in The Biochemical journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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.
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.
Who cites it
8 citing papers in PubMed, 41 citations in OpenAlex.
- Dantrolene inhibition of ryanodine channels (RyR2) in artificial lipid bilayers depends on FKBP12.6.The Journal of general physiology · 2023Article
- Ero1α-Dependent ERp44 Dissociation From RyR2 Contributes to Cardiac Arrhythmia.Circulation research · 2022Article
- A Type 2 Ryanodine Receptor Variant in the Helical Domain 2 Associated with an Impairment of the Adrenergic Response.Journal of personalized medicine · 2021Article
- Proarrhythmic Remodeling of Calcium Homeostasis in Cardiac Disease; Implications for Diabetes and Obesity.Frontiers in physiology · 2018Review
- Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized cardiac myocytes and effects on Ca sparks.Circulation research · 2010Article
- Ryanodine receptor-mediated arrhythmias and sudden cardiac death.Pharmacology & therapeutics · 2009Review
- Mechanisms and potential therapeutic targets for ventricular arrhythmias associated with impaired cardiac calcium cycling.Journal of molecular and cellular cardiology · 2008Review
- Ryanodine receptor regulation by intramolecular interaction between cytoplasmic and transmembrane domains.Molecular biology of the cell · 2004Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ryanodine receptor complex (RyR), a large oligomeric assembly that functions as a Ca(2+)-release channel in the sarcoplasmic reticulum (SR)/endoplasmic reticulum (ER), comprises four RyR subunits and four FK506-binding proteins (FKBP). The precise mode of interaction and modulation of the cardiac RyR (RyR2) channel by FKBP12/FKBP12.6 remains to be fully defined. We have generated a series of Chinese-hamster ovary (CHO) cell lines stably expressing discrete levels of recombinant human RyR2 (hRyR2) (CHO(hRyR2)). Confocal microscopy of CHO(hRyR2) cells co-expressing either FKBP12 or FKBP12.6 demonstrated that FKBP12.6 was sequestered from the cytoplasm to ER membranes as the cellular levels of hRyR2 increased. There was negligible hRyR2-induced subcellular redistribution of FKBP12. The magnitude of Ca(2+) release in CHO(hRyR2) cells in response to stimulation by 4-chloro- m -cresol was in direct proportion to the expression levels of hRyR2. However, in CHO(hRyR2) cells co-expressing FKBP12.6, Ca(2+) release triggered by the addition of 4-chloro- m -cresol was markedly decreased. In contrast, co-expression of FKBP12 did not affect agonist-induced Ca(2+) release in CHO(hRyR2) cells. Resting cytoplasmic [Ca(2+)] in CHO(hRyR2) remained unaltered after co-expression of FKBP12 or FKBP12.6, but estimation of the ER Ca(2+) load status showed that co-expression of FKBP12.6, but not FKBP12, promoted superfilling of the ER Ca(2+) store which could not be released by RyR2 after agonist activation. The effects of FKBP12.6 on hRyR2-mediated intracellular Ca(2+) handling could be antagonized using rapamycin (5 microM). These results suggest that FKBP12.6 associates with hRyR2 in situ to modulate precisely the functionality of hRyR2 Ca(2+)-release channel.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.