By using [3H]-ryanodine binding assay, SDS-PAGE, Western Blotting, photon correlation spectroscopy (PCS) and DPH fluorescence polarization, the influences of oxidation modulators 1,4NQ and Na2SeO3 on the channel activity, the average particle size of RyR1, the distribution of SR proteins in crosslinking complex, and fluidity of SR membrane under the oxidative stress were investigated. The results indicate that, upon to the oxidants treatment of 1,4NQ and Na2SeO3, both the activity of RyR1 channel and the fluidity of SR membrane decreased, and macromolecular crosslinked complexes consisting of RyR1 emerged on the gel of the SR membrane proteins. Further investigations showed that DTT decomposed the crosslinked complexes. Above results suggest that the inhibition of RyR1 channel caused by the high concentration of oxidant modulators is probably due to oxidation of the functional sulfhydryls which are responsible for the closure of the channels, and the occurrence of mistaken crosslinking between SR proteins which would alter the function of the calcium release unit.