Effects of H2O2 on electrical membrane properties of skeletal myotubes

Reactive oxygen species (ROS), normally generated in skeletal muscles, could control excitability of muscle fibers through redox modulation of membrane ion channels. However, the mechanisms of ROS action remain largely unknown. To investigate the action of ROS on electrical properties of muscle cells, patch-clamp recordings were performed after application of hydrogen peroxide (H2O2) to skeletal myotubes. H2O2 facilitated sodium spikes after a hyperpolarizing current pulse, by decreasing the latency for spike initiation. Importantly, the antioxidant N-acetylcysteine induced the opposite effect, suggesting the redox control of muscle excitability. The effect of H2O2 was abolished in the presence of catalase. The kinetics of sodium channels were not affected by H2O2. However, the fast inward rectifier K+ (KIR) currents, activated by hyperpolarization, were reduced by H2O2, similar to the action of the potassium channel blockers Ba2+ and Cs+. The block of the outward tail current contributing to KIR deactivation can explain the shorter latency for spike initiation. We propose that the KIR current is an important target for ROS action in myotubes. Our data would thus suggest that ROS are involved in the control of the excitability of myotubes and, possibly, in the oscillatory behavior critical for the plasticity of developing muscle cells.