Effect of hypoxia on single skeletal muscle fiber contractility at physiological temperature

Abstract

Hypoxia has been associated with an increased reactive oxygen species (ROS) production in contracting skeletal muscle. However, it is not known whether hypoxia can modulate the muscle contractility, particularly at physiological temperature. We hypothesized that a decrease in intracellular PO2 would regulate force in skeletal muscle through ROS. Intact single fast‐twitch fibers from mouse muscle (n=20) were stimulated (1–200 Hz) at ambient PO2 (~150 Torr) and under hypoxia (2–4 Torr) at 22, 32 and 35ºC. At both 22 and 32ºC, hypoxia did not affect contractility. However, at 35ºC under hypoxia, there was a significant (P<0.05) decrease in submaximal tension (28 ± 11%) compared to ambient PO2. Treatment of single myofibers with tiron (1 mM) and N‐acetyl‐cysteine (NAC; 0.5 mM) at low PO2 did not alter the decrease in submaximal force seen during hypoxia. However, with H2O2 (100 μM), submaximal tension increased after 2–5 min (51 ± 4%), and then decreased thereafter. These results suggest that hypoxia at physiological temperature diminishes submaximal force in single fast‐twitch fibers, but not in a ROS dependent manner. Supported by NIH (AR040155‐17) and APS Undergraduate Summer Fellowship.