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American journal of physiology. Regulatory, integrative and comparative physiology

Low Po₂ conditions induce reactive oxygen species formation during contractions in single skeletal muscle fibers.


PMID 23576612

Abstract

Contractions in whole skeletal muscle during hypoxia are known to generate reactive oxygen species (ROS); however, identification of real-time ROS formation within isolated single skeletal muscle fibers has been challenging. Consequently, there is no convincing evidence showing increased ROS production in intact contracting fibers under low Po₂ conditions. Therefore, we hypothesized that intracellular ROS generation in single contracting skeletal myofibers increases during low Po₂ compared with a value approximating normal resting Po₂. Dihydrofluorescein was loaded into single frog (Xenopus) fibers, and fluorescence was used to monitor ROS using confocal microscopy. Myofibers were exposed to two maximal tetanic contractile periods (1 contraction/3 s for 2 min, separated by a 60-min rest period), each consisting of one of the following treatments: high Po₂ (30 Torr), low Po₂ (3-5 Torr), high Po₂ with ebselen (antioxidant), or low Po₂ with ebselen. Ebselen (10 μM) was administered before the designated contractile period. ROS formation during low Po₂ treatment was greater than during high Po₂ treatment, and ebselen decreased ROS generation in both low- and high-Po₂ conditions (P < 0.05). ROS accumulated at a faster rate in low vs. high Po₂. Force was reduced >30% for each condition except low Po₂ with ebselen, which only decreased ~15%. We concluded that single myofibers under low Po₂ conditions develop accelerated and more oxidative stress than at Po₂ = 30 Torr (normal human resting Po₂). Ebselen decreases ROS formation in both low and high Po₂, but only mitigates skeletal muscle fatigue during reduced Po₂ conditions.

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