Skeletal Muscle Inosine Monophosphate Formation Preserves ∆G_ATP During Incremental Step Contractions in Vivo

The cause and consequences of inosine monophosphate (IMP) formation when ATP declines during muscular contractions in vivo are not fully understood. The purpose of this study was to examine the role of IMP formation in the maintenance of the Gibbs free energy for ATP hydrolysis (∆G_ATP) during dynamic contractions of increasing workload, and the implications of ATP loss in vivo. Eight males (27.5, 25-35yr, median, range) completed an 8-minute incremental protocol (2-minute stages of isotonic knee extensions (0.5Hz)) in a 3-Tesla magnetic resonance (MR) system. Phosphorus MR spectra were obtained from the knee extensor muscles at rest and during contractions and recovery. Although the ATP demand during contractions was met primarily by oxidative phosphorylation, [ATP] decreased from 8.2 mM to 7.5 (range 6.4-8.0) mM and [IMP] increased from 0 mM to 0.6 (0.1-1.7) mM. Modeling showed that, in the absence of IMP formation, excess ADP would result in a less favorable ∆G_ATP (p<0.001). Neither [ATP] nor [IMP] had returned to baseline following 10 minutes of recovery (p<0.001). Notably, ∆[ATP] was linearly related to the post-contraction reduction in muscle oxidative capacity (r=0.74, p=0.037). Our results highlight the importance of IMP formation in preserving cellular energy status by avoiding increases in ADP above that necessary to stimulate energy production pathways. However, the consequence of IMP formation was an incomplete recovery of [ATP], which in turn was related to decreased muscle oxidative capacity following contractions. These results likely have implications for the capacity to generate adequate energy during repeated bouts of muscular work.