Intracellular acidification and volume increases explain R(2) decreases in exercising muscle

Exercise-induced decreases in the (1)H transverse relaxation rate (R(2)) of muscle have been well documented, but the mechanism remains unclear. In this study, the hypothesis was tested that R(2) decreases could be explained by pH decreases and apparent intracellular volume (V(i)') increases. (31)P and (1)H spectroscopy, biexponential R(2) analysis, and imaging were performed prior to and following fatiguing exercise in iodoacetate-treated (IAA, to inhibit glycolysis), NaCN-treated (to inhibit oxidative phosphorylation), and untreated frog gastrocnemii. In all exercised muscles, the apparent intracellular R(2) (R(2i)') and pH decreased, while intracellular osmolytes and V(i)' increased. These effects were larger in NaCN-treated and untreated muscles than in IAA-treated muscles. Multiple regression analysis showed that pH and V(i)' changes explain 70% of the R(2i)' variance. Separate experiments in unexercised muscles demonstrated causal relationships between pH and R(2i)' and between V(i)' and R(2i)'. These data indicate that the R(2) change of exercise is primarily an intracellular phenomenon caused by the accumulation of the end-products of anaerobic metabolism. In the NaCN-treated and untreated muscles, the R(2i)' change increased as field strength increased, suggesting a role for pH-modulated chemical exchange.