Photooxidation of skeletal muscle sarcoplasmic reticulum induces rapid calcium release

The photooxidizing xanthene dye rose bengal is shown to induce rapid Ca²⁺ release from skeletal muscle sarcoplasmic reticulum (SR) vesicles. In the presence of light, nanomolar concentrations of rose bengal increase the Ca²⁺ permeability of the SR and stimulate the production of singlet oxygen (¹O₂). In the absence of light, no ¹O₂ production is measured. Under these conditions, higher concentrations of rose bengal (micromolar) are required to stimulate Ca²⁺ release. Furthermore, removal of oxygen from the release medium results in marked inhibition of the light-dependent reaction rate. Rose bengal-induced Ca²⁺ release is relatively insensitive to Mg²⁺. At nanomolar concentrations, rose bengal inhibits [³H]ryanodine binding to its receptor. β,γ-Methyleneadenosine 5′-triphosphate, a nonhydrolyzable analog of ATP, inhibits rose bengal-induced Ca²⁺ release and prevents rose bengal inhibition of [³H]ryanodine binding. Ethoxyformic anhydride, a histidine modifying reagent, at millimolar concentrations induces Ca²⁺ release from SR vesicles in a manner similar to that of rose bengal. The molecular mechanism underlying rose bengal modification of the Ca²⁺ release system of the SR appears to involve a modification of a histidyl residue associated with the Ca²⁺ release protein from SR. The light-depedent reaction appears to be mediated by singlet oxygen.