H2O2 activates ryanodine receptor but has little effect on recovery of releasable Ca2+ content after fatigue

We studied whether hydrogen peroxide (H2O2) at ≤10 μM activates the ryanodine receptor and decreases releasable Ca2+ content in the sarcoplasmic reticulum after fatigue. Exposure of rabbit or frog skeletal muscle ryanodine receptors to 10 μM H2O2 enhanced channel activity in lipid bilayers when the redox potential was defined at cis = −220 mV and trans = −180 mV. Channel activation by 10 μM H2O2 was also observed when cispotential was set at −220 mV without defining transpotential, but the effect was less. Reduction of trans redox potential from −180 to −220 mV did not alter channel activity. H2O2 at 500 μM failed to activate the channel when the redox potential was not controlled. Stimulation of the frog muscle fiber for 2 min (50 Hz, a duty cycle of 200 ms/s) decreased tetanus tension by ∼50%. After 1 min, tetanus recovered rapidly to ∼70% of control and thereafter slowly approached the control level. Amplitudes of caffeine- and 4-chloro-m-cresol-induced contractures were decreased after a 60-min rest. ...