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The absence of dysferlin induces the expression of functional connexin-based hemichannels in human myotubes

Overview of attention for article published in BMC Cell Biology, May 2016
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Title
The absence of dysferlin induces the expression of functional connexin-based hemichannels in human myotubes
Published in
BMC Cell Biology, May 2016
DOI 10.1186/s12860-016-0096-6
Pubmed ID
Authors

Luis A. Cea, Jorge A. Bevilacqua, Christian Arriagada, Ana María Cárdenas, Anne Bigot, Vincent Mouly, Juan C. Sáez, Pablo Caviedes

Abstract

Mutations in the gene encoding for dysferlin cause recessive autosomal muscular dystrophies called dysferlinopathies. These mutations induce several alterations in skeletal muscles, including, inflammation, increased membrane permeability and cell death. Despite the fact that the etiology of dysferlinopathies is known, the mechanism that explains the aforementioned alterations is still elusive. Therefore, we have now evaluated the potential involvement of connexin based hemichannels in the pathophysiology of dysferlinopathies. Human deltoid muscle biopsies of 5 Chilean dysferlinopathy patients exhibited the presence of muscular connexins (Cx40.1, Cx43 and Cx45). The presence of these connexins was also observed in human myotubes derived from immortalized myoblasts derived from other patients with mutated forms of dysferlin. In addition to the aforementioned connexins, these myotubes expressed functional connexin based hemichannels, evaluated by ethidium uptake assays, as opposed to myotubes obtained from a normal human muscle cell line, RCMH. This response was reproduced in a knock-down model of dysferlin, by treating RCMH cell line with small hairpin RNA specific for dysferlin (RCMH-sh Dysferlin). Also, the presence of P2X7 receptor and the transient receptor potential channel, TRPV2, another Ca(2+) permeable channels, was detected in the myotubes expressing mutated dysferlin, and an elevated resting intracellular Ca(2+) level was found in the latter myotubes, which was in turn reduced to control levels in the presence of the molecule D4, a selective Cx HCs inhibitor. The data suggests that dysferlin deficiency, caused by mutation or downregulation of dysferlin, promotes the expression of Cx HCs. Then, the de novo expression Cx HC causes a dysregulation of intracellular free Ca(2+) levels, which could underlie muscular damage associated to dysferlin mutations. This mechanism could constitute a potential therapeutical target in dysferlinopathies.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 30 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 6 20%
Professor 4 13%
Researcher 3 10%
Student > Ph. D. Student 3 10%
Student > Postgraduate 2 7%
Other 7 23%
Unknown 5 17%
Readers by discipline Count As %
Medicine and Dentistry 8 27%
Agricultural and Biological Sciences 6 20%
Biochemistry, Genetics and Molecular Biology 4 13%
Neuroscience 3 10%
Nursing and Health Professions 1 3%
Other 0 0%
Unknown 8 27%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 May 2016.
All research outputs
#7,663,637
of 8,837,009 outputs
Outputs from BMC Cell Biology
#175
of 219 outputs
Outputs of similar age
#228,479
of 274,918 outputs
Outputs of similar age from BMC Cell Biology
#5
of 11 outputs
Altmetric has tracked 8,837,009 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 219 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.2. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 11 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.