High-frequency electrical stimulation reveals a p38-mTOR signaling module correlated with force-time integral

Area of Science:

• Exercise Physiology
• Molecular Biology
• Muscle Physiology

Background:

• High-frequency electrical stimulation (HFES) is known to induce muscle hypertrophy.
• Both mechanical and metabolic stresses contribute to signaling pathways involved in protein synthesis during muscle contraction.
• Understanding the distinct roles of mechanical versus metabolic stress in HFES-induced signaling is crucial for optimizing training protocols.

Purpose of the Study:

• To investigate the immediate signaling responses to mechanical and metabolic stresses induced by HFES.
• To test the hypothesis that HFES primarily stimulates growth-related signaling through mechanical means.
• To identify specific signaling molecules and pathways correlated with mechanical force versus metabolic load during HFES.

Main Methods:

• Mouse tibialis anterior muscle was subjected to HFES with manipulated contraction time (metabolic emphasis) or contraction force (mechanical emphasis).
• Signaling pathway activation was assessed by measuring the phosphorylation of key proteins including p54 JNK, ERK, p70S6k, acetyl-CoA carboxylase, p38, and FAK.
• Factor analysis was employed to identify interconnected signaling modules related to force-time integral (FTI).

Main Results:

• Phosphorylation of p54 JNK, ERK, and p70S6k was independent of FTI when manipulated by contraction time or force.
• Phosphorylation of acetyl-CoA carboxylase correlated with FTI when time was manipulated, while p38 and FAK phosphorylation correlated with FTI when force was manipulated.
• A distinct p38-mTOR signaling module was identified that consistently correlated with FTI, indicating sensitivity to mechanical aspects of contraction.

Conclusions:

• The p38-mTOR signaling module is a key mechanical sensor during HFES, distinct from metabolic stress markers.
• HFES-induced muscle growth signaling appears to be significantly influenced by mechanical load.
• These findings provide insights into the differential signaling responses to mechanical and metabolic stimuli during electrically induced muscle contractions.