Cytotoxicity of phenazine methosulphate on skeletal muscle. The role of the sarcoplasmic reticulum in initiating myofilament damage.

Phenazine methosulphate (PMS) or ferricyanide caused ultrastructural damage, including sarcolemma folds and swelling of the sarcoplasmic reticulum (SR), in amphibian skeletal muscle which corresponds with that triggered by a rise in [Ca]i and which, it is suggested, is caused by the activation of NAD(P)H oxidases at the sarcolemma (where it causes sarcolemma folding) and SR (where it causes myofilament damage). PMS also caused SR swelling and more limited damage in chemically-skinned muscle at zero [Ca]. In contrast with the oxygen paradox of cardiac muscle, there is no evidence for the production of oxygen radicals since no protection was provided by N2, mannitol, desferrioxamine or alpha-tocopherol, nor was the cell damage produced by an influx of Ca across the sarcolemma.