Induction of calcium release from isolated sarcoplasmic reticulum by triphenyltin

A direct peripheral myopathy has been found in organotin intoxication and suggested to be a significant factor in the development of muscle weakness following exposure. In this study, by using the isolated sarcoplasmic reticulum membrane vesicles, we have shown that triphenyltin dose-dependently induced Ca ²⁺ release from the actively and passively loaded sarcoplasmic reticulum vesicles. Triphenyltin induced Ca ²⁺ release in ruthenium red-sensitive and insensitive ways with EC ₅₀ values of 75 and 270 μM, respectively. The Ca ²⁺-ATPase activity and Ca ²⁺ uptake of sarcoplasmic reticulum were also inhibited by triphenyltin. Triphenyltin exerted dual effects on the apparent [ ³H]ryanodine binding. Triphenyltin (0.5-10 μM) dose-dependently potentiated the [ ³H]ryanodine binding; however, the [ ³H] ryanodine binding decreased as the concentration of triphenyltin increased. The dissociation of bound [ ³H] ryanodine was facilitated by triphenyltin. The present study suggested that the internal Ca ²⁺ store of skeletal muscle could be depleted by triphenyltin through the inhibition of the Ca ²⁺ uptake and the induction of Ca ²⁺ release by acting on the Ca ²⁺-ATPase and Ca ²⁺ release channel, also known as the ryanodine receptor, of sarcoplasmic reticulum, respectively. These results could partly explain the development of muscle weakness in organotin intoxication; however, their relevance to the development of peripheral myopathy requires further examination.