pH-Resolved ATP Synthesis in Skeletal Muscle: Concept, Implementation, and Assessment Using Dynamic ³¹P Magnetic...

Area of Science:

• Muscle physiology
• Metabolic energetics
• Biophysics

Background:

• Skeletal muscle energetics and ATP synthesis are dynamic during exercise recovery.
• Conventional models overlook myofiber heterogeneity and pH effects on metabolism.
• Proton magnetic resonance spectroscopy (31P MRS) is crucial for assessing muscle metabolism.

Purpose of the Study:

• To investigate the relationship between pH, inorganic phosphate (Pi), and phosphocreatine (PCr) during muscle recovery.
• To develop a novel analytical method for pH-resolved ATP synthesis assessment using 31P MRS.
• To characterize metabolic heterogeneity in skeletal muscle.

Main Methods:

• Dynamic 31P MRS scans during plantar flexion exercise in five healthy subjects.
• ATP synthesis evaluation using single-pool and multi-pool models based on PCr and Pi recovery.
• Multi-pool model segmented Pi signal into four pH-specific pools (pH 7.3, 7.0, 6.8, 6.6).

Main Results:

• Single-pool model showed monoexponential PCr and Pi recovery post-exercise (τPi: 33±9s, τPCr: 40±9s) and a pH "heart-beat" pattern.
• Multi-pool model revealed significant pH-dependent Pi recovery, slowing at lower pH values (τPi: 19±6s at pH 7.3 to 46±17s at pH 6.6).
• Aging slowed Pi recovery under acidic conditions, with minimal effect at neutral/alkaline pH.

Conclusions:

• A multi-pool framework overcomes single-pool model limitations for ATP synthesis assessment.
• The study demonstrates pH-dependent ATP synthesis and significant metabolic heterogeneity in skeletal muscle.
• Findings provide insights into how myofiber microenvironments influence ATP synthesis during exercise and recovery.