Evidence map›Paper›PMID 24969422›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Impaired functional communication between the L-type calcium channel and mitochondria contributes to metabolic inhibition in the mdx heart.

Helena M Viola, Abbie M Adams, Stefan M K Davies, Susan Fletcher, Aleksandra Filipovska, Livia C Hool

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

39 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Novel Drug Targets in Diastolic Heart Disease.International journal of molecular sciences · 2025
    Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. TRPM2-mediated CaCell communication and signaling : CCS · 2023
    Review
  11. Review
  12. Article
  13. How cytoskeletal proteins regulate mitochondrial energetics in cell physiology and diseases.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022
    Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Article
  19. Characterization and validation of a preventative therapy for hypertrophic cardiomyopathy in a murine model of the disease.Proceedings of the National Academy of Sciences of the United States of America · 2020
    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

6 authors at 3 institutions in 1 country.

Helena M ViolaSchool of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, WA 6009, Australia;
Abbie M AdamsWestern Australian Neuroscience Research Institute and Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, QEII Medical Centre, Nedlands, WA 6009, Australia;
Stefan M K DaviesHarry Perkins Institute for Medical Research, The University of Western Australia, Perth, WA 6000, Australia;
Susan FletcherWestern Australian Neuroscience Research Institute and Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, QEII Medical Centre, Nedlands, WA 6009, Australia;Centre for Comparative Genomics, Murdoch University, Murdoch, WA 6150, Australia; and.
Aleksandra FilipovskaHarry Perkins Institute for Medical Research, The University of Western Australia, Perth, WA 6000, Australia;
Livia C HoolSchool of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, WA 6009, Australia;Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia livia.hool@uwa.edu.au.
University of Western Australia · AUHarry Perkins Institute of Medical Research · AUMurdoch University · AU

Funding

NINDS NIH HHS 5R01NS04414606
6 · The paper itself

Abstract

Duchenne muscular dystrophy is a fatal X-linked disease characterized by the absence of dystrophin. Approximately 20% of boys will die of dilated cardiomyopathy that is associated with cytoskeletal protein disarray, contractile dysfunction, and reduced energy production. However, the mechanisms for altered energy metabolism are not yet fully clarified. Calcium influx through the L-type Ca(2+) channel is critical for maintaining cardiac excitation and contraction. The L-type Ca(2+) channel also regulates mitochondrial function and metabolic activity via transmission of movement of the auxiliary beta subunit through intermediate filament proteins. Here, we find that activation of the L-type Ca(2+) channel is unable to induce increases in mitochondrial membrane potential and metabolic activity in intact cardiac myocytes from the murine model of Duchenne muscular dystrophy (mdx) despite robust increases recorded in wt myocytes. Treatment of mdx mice with morpholino oligomers to induce exon skipping of dystrophin exon 23 (that results in functional dystrophin accumulation) or application of a peptide that resulted in block of voltage-dependent anion channel (VDAC) "rescued" mitochondrial membrane potential and metabolic activity in mdx myocytes. The mitochondrial VDAC coimmunoprecipitated with the L-type Ca(2+) channel. We conclude that the absence of dystrophin in the mdx ventricular myocyte leads to impaired functional communication between the L-type Ca(2+) channel and mitochondrial VDAC. This appears to contribute to metabolic inhibition. These findings provide new mechanistic and functional insight into cardiomyopathy associated with Duchenne muscular dystrophy.

Indexed as

Membrane Potential, MitochondrialAnimalsCalciumCalcium Channels, L-TypeDystrophinExonsHeart VentriclesMaleMiceMice, Inbred mdxMitochondrial MembranesMorpholinosMuscular Dystrophy, DuchenneMyocardiumMyocytes, CardiacCalciumCalcium Channels, L-TypeDystrophinMorpholinoscytoskeletonion channelsstructure

Identifiers

PMID24969422
PMCPMC4104855
OpenAlexW1980810115

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.