Muscle contraction requires the physiology to adapt rapidly to meet the surge in energy demand. To investigate the shift in metabolic control, especially between oxygen and metabolism, researchers often depend on near-infrared spectroscopy (NIRS) to measure noninvasively the tissue O₂. Because NIRS detects the overlapping myoglobin (Mb) and hemoglobin (Hb) signals in muscle, interpreting the data as an index of cellular or vascular O₂requires deconvoluting the relative contribution. Currently, many in the NIRS field ascribe the signal to Hb. In contrast,¹H NMR has only detected the Mb signal in contracting muscle, and comparative NIRS and NMR experiments indicate a predominant Mb contribution. The present study has examined the question of the NIRS signal origin by measuring simultaneously the¹H NMR,³¹P NMR, and NIRS signals in finger flexor muscles during the transition from rest to contraction, recovery, ischemia, and reperfusion. The experiment results confirm a predominant Mb contribution to the NIRS signal from muscle. Given the NMR and NIRS corroborated changes in the intracellular O₂, the analysis shows that at the onset of muscle contraction, O₂declines immediately and reaches new steady states as contraction intensity rises. Moreover, lactate formation increases even under quite aerobic condition.

The purpose of this study was to investigate the effects of a partial suppression of monocarboxylate transporter (MCT)‐1 on skeletal muscle pH, energetics, and function (MCT1 ^{+/ −} mice). Twenty‐four MCT1 ^{+/ −} and 13 wild‐type (WT) mice were subjected to a rest–exercise–recovery protocol, allowing assessment of muscle energetics (by magnetic resonance spectroscopy) and function. The study included analysis of enzyme activities and content of protein involved in pH regulation. Skeletal muscle of MCT1 ^{+/ −} mice had lower MCT1 (‐61%; P < 0.05) and carbonic anhydrase (CA)‐II (‐54%; P < 0.05) contents. Although intramuscular pH was higher in MCT1 ^{+/ −} mice at rest ( P < 0.001), the mice showed higher acidosis during the first minute of exercise ( P < 0.01). Then, the pH time course was similar among groups until exercise completion. MCT1 ^{+/ −} mice had higher specific peak ( P < 0.05) and maximum tetanic ( P < 0.01) forces and lower fatigability ( P < 0.001) when compared to WT mice. We conclude that both MCT1 and CAII are involved in the homeostatic control of pH in skeletal muscle, both at rest and at the onset of exercise. The improved muscle function and resistance to fatigue in MCT1 ^{+/ −} mice remain unexplained.—Chatel, B., Bendahan, D., Hourdé, C., Pellerin, L., Lengacher, S., Magistretti, P., Fur, Y. L., Vilmen, C., Bernard, M., Messonnier, L. A. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice. FASEB J. 31, 2562–2575 (2017). www.fasebj.org

Sickle cell disease (SCD) is associated with an impaired oxygen delivery to skeletal muscle that could alter ATP production processes. The present study aimed to determine the effects of sickle hemoglobin (HbS) on muscle pH homeostasis in response to exercise in homozygous (HbSS, n = 9) and heterozygous (HbAS, n = 10) SCD (Townes) mice in comparison to control (HbAA, n = 10) littermates. Magnetic resonance spectroscopy of phosphorus 31 enabled to measure intramuscular pH and phosphocreatine (PCr) concentration during rest-stimulation-recovery protocols at two different intensities. Maximal activity of some enzymes involved in muscle energetics and content of proteins involved in pH regulation were also investigated. HbSS mice presented a more pronounced exercise-induced intramuscular acidosis, whatever the intensity of exercise. Moreover, the depletion of PCr was also exacerbated in HbSS mice in response to intense exercise as compared with both HbAA and HbAS mice (P < 0.01). While no difference was observed concerning proteins involved in muscle pH regulation, the activity of enolase (a glycolytic enzyme) was higher in both HbSS and HbAS mice as compared with controls (P < 0.05). Interestingly, HbAS mice presented also metabolic impairments as compared with their control counterparts. This study has identified for the first time an exacerbated exercise-induced intramuscular acidosis in SCD mice. NEW & NOTEWORTHY The main finding of the present study was that the exercise-induced intramuscular acidosis was systematically more pronounced in sickle cell disease (SCD) mice as compared with their control counterparts. This result is important since it has been demonstrated in vitro that acidosis can trigger hemoglobin polymerization. From that point of view, our results tend to support the idea that high-intensity exercise may increase the risk of hemoglobin polymerization in SCD.