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Defined electrical stimulation emphasizing excitability for the development and testing of engineered skeletal muscle
Alastair Khodabukus1, Keith Baar
1Division of Neurobiology, Physiology and Behavior, University of California Davis, Davis, California, USA.
Tissue Engineering. Part C, Methods
|November 19, 2011
Summary
Electrical stimulation is crucial for muscle development, but excessive pulse amplitude can cause damage. Optimal stimulation uses lower electric fields to enhance engineered muscle function without impairment.
Area of Science:
- Biomedical Engineering
- Muscle Physiology
- Tissue Engineering
Background:
- Electrical stimulation is essential for skeletal muscle maturation and monitoring development.
- Incorrect stimulation parameters can lead to electrochemical damage, hindering muscle regeneration.
- Understanding optimal stimulation is key for effective muscle tissue engineering.
Purpose of the Study:
- To determine if pulse amplitude or pulse width causes detrimental effects on engineered muscle.
- To investigate engineered muscle response to continuous 24-hour electrical stimulation.
- To identify safe electrical stimulation parameters for muscle development.
Main Methods:
- Engineered muscle tissue was subjected to varying electrical stimulation parameters (pulse amplitude and width).
- Acute and continuous (24-hour) stimulation protocols were employed.
- Muscle function was assessed by measuring force, half-relaxation time, and fatigability.
- The role of mammalian target of rapamycin (mTORC1) in response to stimulation was evaluated using rapamycin (RAP).
Main Results:
- Acute stimulation above six-times rheobase significantly increased half-relaxation time and fatigability.
- Lengthening pulse width did not cause negative effects, indicating damage is amplitude-dependent.
- Continuous stimulation (>0.5 V/mm) increased force by ~2.5-fold.
- Forty percent of the force increase was mTORC1-dependent; the remainder was attributed to cytoskeletal rearrangement.
Conclusions:
- Electrochemical damage to engineered muscle occurs at electric fields at or above six-times rheobase.
- Optimal muscle stimulation should utilize lower electric fields (two- to four-times rheobase).
- Continuous stimulation can enhance muscle force through mTORC1-dependent and independent mechanisms.
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