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 Ca²⁺ release from the actively and passively loaded sarcoplasmic reticulum vesicles. Triphenyltin induced Ca²⁺ release in ruthenium red-sensitive and insensitive ways with EC₅₀ values of 75 and 270 μM, respectively. The Ca²⁺-ATPase activity and Ca²⁺ 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 Ca²⁺ store of skeletal muscle could be depleted by triphenyltin through the inhibition of the Ca²⁺ uptake and the induction of Ca²⁺ release by acting on the Ca²⁺-ATPase and Ca²⁺ 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.