Skeletal muscle inosine monophosphate formation preserves ΔGATP during incremental step contractions in vivo.

Abstract

The cause and consequences of inosine monophosphate (IMP) formation when adenosine triphosphate (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 (ΔG_ATP) during dynamic contractions of increasing workload and the implications of ATP loss in vivo. Eight males (median 27.5, 25-35 yr range) completed an 8-min incremental protocol [2-min stages of isotonic knee extensions (0.5 Hz)] in a 3-T 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 adenosine diphosphate (ADP) would result in a less favorable ΔG_ATP (P < 0.001). Neither [ATP] nor [IMP] had returned to baseline following 10 min of recovery (P < 0.001). Notably, Δ[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.NEW & NOTEWORTHY An ∼9% decline in [ATP] led to the formation of inosine monophosphate (IMP) during submaximal muscular contractions. Modeling revealed IMP formed to preserve a favorable energy state (ΔG_ATP) by minimizing large increases in [ADP], whereas the loss of [ATP] did not alter ΔG_ATP. [ATP] did not recover by 10 min, and the loss of [ATP] was associated with a reduced oxidative capacity, providing a new link between [ATP] loss and an impaired energetic capacity in vivo.