Evidence map›Paper›PMID 21482776›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2011

Orthograde dihydropyridine receptor signal regulates ryanodine receptor passive leak.

José Miguel Eltit, Hongli Li, Christopher W Ward, Tadeusz Molinski, Isaac N Pessah, Paul D Allen, José R Lopez

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

34 citing papers in PubMed, 53 citations in OpenAlex.

  1. Pathogenic CaCommunications biology · 2026
    Article
  2. Review
  3. Article
  4. Article
  5. Interplay between MgNature communications · 2024
    Article
  6. CaHandbook of experimental pharmacology · 2023
    Article
  7. Article
  8. Article
  9. CaCells · 2019
    Review
  10. Postsynaptic CaScientific reports · 2019
    Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. De novo reconstitution reveals the proteins required for skeletal muscle voltage-induced CaProceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  16. Congenital myopathy results from misregulation of a muscle Ca2+ channel by mutant Stac3.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  17. Review of RyR1 pathway and associated pathomechanisms.Acta neuropathologica communications · 2016
    Review
  18. Article
  19. Article
  20. Review
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 5 institutions in 2 countries.

José Miguel EltitDepartment of Anesthesiology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Hongli Li
Christopher W Ward
Tadeusz Molinski
Isaac N Pessah
Paul D Allen
José R Lopez
Brigham and Women's Hospital · USArmy Medical University · CNUniversity of California, Davis · USUniversity of Maryland, Baltimore · USUniversity of Montana · US

Funding

Uncovering the Molecular Basis of Malignant HyperthermiaP01AR052354 · NIAMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI FRANZINI-ARMSTRONG, CLARA · 2006 to 2016
$13.4M
Structure Function Studies of RyR1 in a Myogenic KnockoutR01AR043140 · NIAMS · CHILDREN'S HOSPITAL BOSTON · PI ALLEN, PAUL D · 1996 to 2010
$4.8M
NIAMS NIH HHS 2R01AR43140NIAMS NIH HHS 5P01 AR052354NIAMS NIH HHS P01 AR052354NIAMS NIH HHS R01 AR043140
6 · The paper itself

Abstract

The skeletal muscle dihydropyridine receptor (DHPR) and ryanodine receptor (RyR1) are known to engage a form of conformation coupling essential for muscle contraction in response to depolarization, referred to as excitation-contraction coupling. Here we use WT and Ca(V)1.1 null (dysgenic) myotubes to provide evidence for an unexplored RyR1-DHPR interaction that regulates the transition of the RyR1 between gating and leak states. Using double-barreled Ca(2+)-selective microelectrodes, we demonstrate that the lack of Ca(V)1.1 expression was associated with an increased myoplasmic resting [Ca(2+)] ([Ca(2+)](rest)), increased resting sarcolemmal Ca(2+) entry, and decreased sarcoplasmic reticulum (SR) Ca(2+) loading. Pharmacological control of the RyR1 leak state, using bastadin 5, reverted the three parameters to WT levels. The fact that Ca(2+) sparks are not more frequent in dysgenic than in WT myotubes adds support to the hypothesis that the leak state is a conformation distinct from gating RyR1s. We conclude from these data that this orthograde DHPR-to-RyR1 signal inhibits the transition of gated RyR1s into the leak state. Further, it suggests that the DHPR-uncoupled RyR1 population in WT muscle has a higher propensity to be in the leak conformation. RyR1 leak functions are to keep [Ca(2+)](rest) and the SR Ca(2+) content in the physiological range and thus maintain normal intracellular Ca(2+) homeostasis.

Indexed as

AnimalsCalciumCalcium Channels, L-TypeCalcium SignalingHalogenated Diphenyl EthersIon Channel GatingMiceMice, Mutant StrainsMuscle ContractionMuscle Fibers, SkeletalRyanodine Receptor Calcium Release ChannelSarcolemmabastadin 5CACNA1S protein, mouseCalciumCalcium Channels, L-TypeHalogenated Diphenyl EthersRyanodine Receptor Calcium Release Channel

Identifiers

PMID21482776
PMCPMC3084091
OpenAlexW2076269741

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.