Human skeletal muscle intracellular oxygenation: the impact of ambient oxygen availability

Intracellular oxygen (O2) availability and the impact of ambient hypoxia have far reaching ramifications in terms of cell signalling and homeostasis; however, in vivo cellular oxygenation has been an elusive variable to assess. Within skeletal muscle the extent to which myoglobin desaturates (deoxy-Mb) and the extent of this desaturation in relation to O2 availability provide an endogenous probe for intracellular O2 partial pressure (P(iO2)). By combining proton nuclear magnetic resonance spectroscopy (1H NMRS) at a high field strength (4 T), assessing a large muscle volume in a highly efficient coil, and extended signal averaging (30 min) we assessed the level of skeletal muscle deoxy-Mb in 10 healthy men (30 +/- 4 years) at rest in both normoxia and hypoxia (10% O2). In normoxia there was an average deoxy-Mb signal of 9 +/- 1%, which, when converted to P(iO2) using an O2/Mb half-saturation (P50) of 3.2 mmHg, revealed an P(iO2) of 34 +/- 6 mmHg. In ambient hypoxia the deoxy-Mb signal rose to 13 +/- 3% (P(iO2) = 23 +/- 6 mmHg). However, intersubject variation in the defence of arterial oxygenation (S(aO2)) in hypoxia (S(aO2) range: 86-67%) revealed a significant relationship between the changes in S(aO2) and P(iO2)(r2 = 0.5). These data are the first to document resting intracellular oxygenation in human skeletal muscle, highlighting the relatively high P(iO2) values that contrast markedly with those previously recorded during exercise (approximately 2-5 mmHg). Additionally, the impact of ambient hypoxia on P(iO2) and the relationship between changes in S(aO2) and P(iO2) stress the importance of the O2 cascade from air to cell that ultimately effects O2 availability and O2 sensing at the cellular level.