Ions, transport, and energetics in normal and diseased skeletal muscle

Abstract

Magnetic resonance spectroscopy (MRS) has highlighted the relationship between intracellular ionic homeostasis and the control of muscle energetics. In skeletal muscle, the oxidative rate of ATP synthesis is largely controlled by ADP, the concentration of which is determined by the creatine kinase equilibrium that includes the concentration of H+. At the onset of aerobic dynamic exercise, ATP is maintained largely by glycolysis, producing lactic acid and PCr breakdown. Vasodilation follows and ATP synthesis becomes predominantly oxidative. During recovery, PCr resynthesis gives a measure of mitochondrial function, and pH recovery reflects the Na+:H+ antiport activity. Dynamic31P MRS measurements can be used to derive quantitative information about the processes (fluxes and concentrations) described above. In diseased muscle (e.g., mitochondrial myopathy, dystrophy, hypertension) specific changes are observed in some of the control functions, ionic fluxes, or mitochondrial oxidative rates.