This study will use in vivo 31P- and 1H-NMR spectroscopy to, first, define the relationships among changes in energetically important metabolites (e.g., PCr, ATP, inorganic phosphate, lactic acid, pH) during and after contractions in intact mammalian skeletal muscle, and second, examine the functional role of these changes in regulation of metabolism and contractile characteristics. Specific issues addressed include: 1. Are there discrepancies between changes in phosphate metabolites observed by NMR which indicate the existence of metabolic microcompartments in muscle? 2. Do changes in PCr and lactic acid quantitatively account for the pH changes observed in muscle during and after brief series of contractions? 3. To what extend does lactate efflux limit the recovery of intracellular pH after a fatiguing series of contractions? 4. How do changes in intracellular pH influence contraction characteristics and metabolic regulation in mammalian muscle? 5. Can changes in ADP, or other adenine nucleotides account for the regulation of respiration in mammalian muscle? A key feature of the study is the comparison of NMR results in different mammalian fiber types, which is made possible by study of isolated, perfused cat biceps brachii (fast-twitch) and soleus (slow-twitch) muscles, and by spatial resolution of NMR spectra from the rat hindlimb. Given the heterogeneity and variability of fiber type in human muscle, this provides essential information for the clinical application of NMR spectroscopy to studies of normal and diseased human muscle.
