Disrupted Membrane Structure and Intracellular Ca2+ Signaling in Adult Skeletal Muscle with Acute Knockdown of Bin1
2011

The Role of Bin1 in Muscle Cell Function

Sample size: 4 publication 10 minutes Evidence: moderate

Author Information

Author(s): Tjondrokoesoemo Andoria, Park Ki Ho, Ferrante Christopher, Komazaki Shinji, Lesniak Sebastian, Brotto Marco, Ko Jae-Kyun, Zhou Jingsong, Weisleder Noah, Ma Jianjie

Primary Institution: Department of Physiology and Biophysics, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey (UMDNJ), Piscataway, New Jersey, United States of America

Hypothesis

Bin1 is essential for maintaining t-tubule structure and Ca2+ homeostasis in adult skeletal muscle.

Conclusion

Knockdown of Bin1 in adult skeletal muscle disrupts t-tubule structure and impairs intracellular Ca2+ signaling.

Supporting Evidence

  • Bin1 is crucial for the maintenance of t-tubule structure in adult skeletal muscle.
  • Reduced Bin1 expression leads to compromised coupling between dihydropyridine receptors and ryanodine receptors.
  • Knockdown of Bin1 resulted in altered intracellular calcium release dynamics.
  • Disruption of t-tubule structure was observed in muscle fibers with reduced Bin1 levels.
  • Voltage-induced calcium release was significantly lower in shRNA-Bin1 fibers compared to controls.
  • Ca2+ spark frequency was reduced in shRNA-Bin1 fibers, indicating impaired calcium signaling.
  • Reduced total calcium stores were measured in shRNA-Bin1 fibers compared to controls.
  • Bin1 knockdown in adult skeletal muscle provides insights into potential myopathy mechanisms.

Takeaway

Bin1 helps keep muscle cells healthy by making sure they can release calcium properly, and when it's missing, the muscle doesn't work as well.

Methodology

The study used in vivo electroporation to deliver shRNA targeting Bin1 to adult mouse skeletal muscle and assessed the effects on t-tubule structure and Ca2+ signaling.

Potential Biases

Potential bias in the interpretation of results due to the use of a single model organism and specific experimental conditions.

Limitations

The study primarily focused on a specific gene knockdown and may not account for compensatory mechanisms in muscle physiology.

Participant Demographics

Adult male wild-type mice from C57Bl/J6 background, aged 3-6 months.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0025740

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