On the role of skeletal muscle acidosis and inorganic phosphates as determinants of central and peripheral fatigue: A 31P‐MRS study

Abstract Intramuscular hydrogen ion (H + ) and inorganic phosphate (Pi) concentrations were dissociated during exercise to challenge their relationships with peripheral and central fatigue in vivo . Ten recreationally active, healthy men (27 ± 5 years; 180 ± 4 cm; 76 ± 10 kg) performed two consecutive intermittent isometric single‐leg knee‐extensor trials (60 maximal voluntary contractions; 3 s contraction, 2 s relaxation) interspersed with 5 min of rest. Phosphorus magnetic resonance spectroscopy ( 31 P‐MRS) was used to continuously quantify intramuscular H + and Pi during both trials. Using electrical femoral nerve stimulation, quadriceps twitch force ( Q tw ) and voluntary activation (VA) were quantified at rest and throughout both trials. Decreases in Q tw and VA from baseline were used to determine peripheral and central fatigue, respectively. Q tw was strongly related to both H + (β coefficient: −0.9, P < 0.0001) and Pi (−1.1, P < 0.0001) across trials. There was an effect of trial on the relationship between Q tw and H + (−0.5, P < 0.0001), but not Q tw and Pi (0.0, P = 0.976). This suggests that, unlike the unaltered association with Pi, a given level of peripheral fatigue was associated with a different H + in Trial 1 vs . Trial 2. VA was related to H + (−0.3, P < 0.0001), but not Pi (−0.2, P = 0.243), across trials and there was no effect of trial (−0.1, P = 0.483). Taken together, these results support intramuscular Pi as a primary cause of peripheral fatigue, and muscle acidosis, probably acting on group III/IV muscle afferents in the interstitial space, as a contributor to central fatigue during exercise. image Key points We investigated the relationship between intramuscular metabolites and neuromuscular function in humans performing two maximal, intermittent, knee‐extension trials interspersed with 5 min of rest. Concomitant measurements of intramuscular hydrogen (H + ) and inorganic phosphate (Pi) concentrations, as well as quadriceps twitch‐force ( Q tw ) and voluntary activation (VA), were made throughout each trial using phosphorus magnetic resonance spectroscopy ( 31 P‐MRS) and electrical femoral nerve stimulations. Although Pi fully recovered prior to the onset of the second trial, H + did not. Q tw was strongly related to both H + and Pi across both trials. However, the relationship between Q tw and H + shifted leftward from the first to the second trial, whereas the relationship between Q tw and Pi remained unaltered. VA was related to H + , but not Pi, across both trials. These in vivo findings support the hypotheses of intramuscular Pi as a primary cause of peripheral fatigue, and muscle acidosis, probably acting on group III/IV muscle afferents, as a contributor to central fatigue.