Acidosis inhibits oxidative phosphorylation in contracting human skeletal muscle in vivo

Abstract

This study tested the hypothesis that acidic pH inhibits oxidative ATP supply during exercise in hand (first dorsal interosseus, FDI) and lower limb (leg anterior compartment, LEG) muscles. We measured oxidative flux and estimated mitochondrial capacity using the changes in creatine phosphate concentration ([PCr]) and pH as detected by 31P magnetic resonance (MR) spectroscopy during isometric exercise and recovery. The highest oxidative ATP flux in sustained exercise was about half the estimated mitochondrial capacity in the LEG (0.38 +/- 0.06 vs. 0.90 +/- 0.14 mM ATP s(-1), respectively), but at the estimated capacity in the FDI (0.61 +/- 0.05 vs. 0.61 +/- 0.09 mM ATP s(-1), respectively). During sustained exercise at a higher contraction rate, intracellular acidosis (pH < 6.88) prevented a rise in oxidative flux in the LEG and FDI despite significantly increased [ADP]. We tested whether oxidative flux could increase above that achieved in sustained exercise by raising [ADP] (> 0.24 mM) and avoiding acidosis using burst exercise. This exercise raised oxidative flux (0.69 +/- 0.05 mM ATP s(-1)) to nearly twice that found with sustained exercise in the LEG and matched (0.65 +/- 0.11 mM ATP s(-1)) the near maximal flux seen during sustained exercise in the FDI. Thus both muscles reached their highest oxidative fluxes in the absence of acidosis. These results show that acidosis inhibits oxidative phosphorylation in vivo and can limit ATP supply in exercising muscle to below the mitochondrial capacity.

Figures

Figure 1. 31P MR spectra from the leg anterior compartment (LEG) and first dorsal interosseous (FDI) muscles of one subject

Spectra shown are from muscle at rest (left) and during sustained exercise with the highest oxidative flux (right).

Figure 2. [PCr] in the LEG and FDI of one subject during sustained exercise bouts

Exercise intensity was incremented by increasing the rate of muscle contractions.

Figure 3. Initial [PCr] and pH in the LEG of one subject after sustained exercise

These data were used to calculate the glycolytic (eqn (1)) and oxidative fluxes (eqn (2)). Time 0 is the end of exercise and data are collected at 6 s intervals. The first recovery point represents an average over 6 s and is reported at 3 s. Each subsequent data point thereafter is reported in 6 s intervals.

Figure 4. Oxidative flux in the LEG and FDI at the end of sustained exercise bouts

Exercise intensity was incremented by increasing the rate of muscle contractions. This figure shows the resulting oxidative flux at two exercise levels below (steps 1 and 2) and at the sustained exercise with the highest oxidative flux (step 3), as well as at the next higher exercise level (step 4). Data are group means ±s.e.m.

Figure 5. [PCr], [ADP] and pH during sustained exercise of the LEG and FDI

Data points represent 30 s averages. The open symbols are the sustained exercise with the highest oxidative flux and the filled symbols are for a higher exercise level. Values are group means; error bars are omitted for clarity.

Figure 6. Oxidative flux, [ADP] and pH at the end of exercise for the LEG and FDI

Open bars are the sustained exercise with the highest oxidative flux and filled bars are a higher exercise level. Values are means; * significant difference between the two exercise conditions.

Figure 7. [PCr], pH and [ADP] during a typical 24 s bout of burst exercise by the LEG

Time 0 is the onset of exercise. The first time point represents an average over 6 s and is reported at 3 s. Each subsequent data point is reported at 6 s intervals.

Figure 8. Oxidative flux, [ADP] and pH for the sustained exercise with the highest oxidative flux (open bars) and for the burst exercise (filled bars)

The dashed horizontal line indicates the estimated mitochondrial oxidative capacity (see eqn (4)). This line is not seen for the FDI since it corresponds to the top of the columns for both exercise protocols. Values are means; * significant difference between the two exercise conditions.