Streptomycin decreases the functional shift to a slow phenotype induced by electrical stimulation in engineered muscle

Alastair Khodabukus, Keith Baar

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Chronic low-frequency stimulation (CLFS) has long been used to induce a fast-to-slow phenotype shift in skeletal muscle. In this study, we explore the role of frequency (10 and 20 Hz), active time (15-60%), and streptomycin in inducing a fast-to-slow shift in engineered muscle. We found that C2C12 engineered muscle could respond to CLFS with an adult-like active time of 60% and found that a constant 10 Hz train of 0.6 s, followed by 0.4 s rest, induced a partial fast-to-slow phenotype shift. Following 2 weeks of CLFS, time-to-peak tension (TPT) (control [CTL]=40.9±0.2 ms; 10 Hz=58.5±3.5 ms; 20 Hz=48.2±2.7 ms) and half-relaxation time (1/2RT) (CTL=50.4±0.6 ms; 10 Hz=76.1±3.3 ms; 20 Hz=66.6±2.3 ms) slowed significantly in frequency, but not in an active time-dependent manner. Streptomycin significantly blunted the slowing of TPT and 1/2RT induced by CLFS by minimizing the fast-to-slow shift in SERCA isoform. Streptomycin (Nonstim=-42.8%±2.5%; Stim=-38.1%±3.6%) significantly prevented the improvement in fatigue resistance seen in CTL constructs (Nonstim=-58.4%±3.6%; Stim=-27.8%±1.7%). Streptomycin reduced the increase seen in GLUT4 protein following CLFS (CTL=89.4%±6.7%; STREP=41.0%±4.3%) and prevented increases in the mitochondrial proteins succinate dehydrogenase (SDH) and ATP synthase. These data demonstrate that streptomycin significantly blunts the fast-to-slow shift induced by CLFS. In the absence of streptomycin, CLFS induced slowing of contractile dynamics and improved fatigue resistance and suggests that this model can be used to study the mechanisms underlying CLFS-induced adaptations in muscle phenotype.

Original languageEnglish (US)
Pages (from-to)1003-1012
Number of pages10
JournalTissue Engineering - Part A
Volume21
Issue number5-6
DOIs
StatePublished - Mar 1 2015

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Streptomycin
Electric Stimulation
Muscle
Phenotype
Muscles
Fatigue of materials
Proteins
Fatigue
Adenosinetriphosphate
Glucose Transporter Type 4
Relaxation time
Succinate Dehydrogenase
Mitochondrial Proteins
Protein Isoforms
Skeletal Muscle
Adenosine Triphosphate

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomedical Engineering
  • Biomaterials

Cite this

Streptomycin decreases the functional shift to a slow phenotype induced by electrical stimulation in engineered muscle. / Khodabukus, Alastair; Baar, Keith.

In: Tissue Engineering - Part A, Vol. 21, No. 5-6, 01.03.2015, p. 1003-1012.

Research output: Contribution to journalArticle

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abstract = "Chronic low-frequency stimulation (CLFS) has long been used to induce a fast-to-slow phenotype shift in skeletal muscle. In this study, we explore the role of frequency (10 and 20 Hz), active time (15-60{\%}), and streptomycin in inducing a fast-to-slow shift in engineered muscle. We found that C2C12 engineered muscle could respond to CLFS with an adult-like active time of 60{\%} and found that a constant 10 Hz train of 0.6 s, followed by 0.4 s rest, induced a partial fast-to-slow phenotype shift. Following 2 weeks of CLFS, time-to-peak tension (TPT) (control [CTL]=40.9±0.2 ms; 10 Hz=58.5±3.5 ms; 20 Hz=48.2±2.7 ms) and half-relaxation time (1/2RT) (CTL=50.4±0.6 ms; 10 Hz=76.1±3.3 ms; 20 Hz=66.6±2.3 ms) slowed significantly in frequency, but not in an active time-dependent manner. Streptomycin significantly blunted the slowing of TPT and 1/2RT induced by CLFS by minimizing the fast-to-slow shift in SERCA isoform. Streptomycin (Nonstim=-42.8{\%}±2.5{\%}; Stim=-38.1{\%}±3.6{\%}) significantly prevented the improvement in fatigue resistance seen in CTL constructs (Nonstim=-58.4{\%}±3.6{\%}; Stim=-27.8{\%}±1.7{\%}). Streptomycin reduced the increase seen in GLUT4 protein following CLFS (CTL=89.4{\%}±6.7{\%}; STREP=41.0{\%}±4.3{\%}) and prevented increases in the mitochondrial proteins succinate dehydrogenase (SDH) and ATP synthase. These data demonstrate that streptomycin significantly blunts the fast-to-slow shift induced by CLFS. In the absence of streptomycin, CLFS induced slowing of contractile dynamics and improved fatigue resistance and suggests that this model can be used to study the mechanisms underlying CLFS-induced adaptations in muscle phenotype.",
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