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Effects of Ca2+-induced Ca2+ release blockers, ruthenium red (RR) and Mg2+, on Ag+-induced Ca2+ release were studied using skinned muscle fibers or fragmented heavy SR (HSR) prepared from frog muscle, and compared with those on caffeine-induced one. Exposure of the skinned fibers to 5 microM Ag+ produced a rapid and large contraction in the presence of 0.043 mM free Mg2+. When Mg2+ concentration was increased to 0.86 mM, Ag+ led to a large transient contraction, combined with a small tonic one. The transient component was completely blocked by high Mg2+ (3.64 mM), but the tonic one was not. Ca2+-ATPase activity was not stimulated by increase of Mg2+ from 0.86 to 3.64 mM. Ag+ and caffeine induced a rapid Ca2+ efflux from HSR in a dose-dependent manner. RR over a range from 1 to 10 microM dose-dependently inhibited the Ca2+ efflux induced by 10 microM Ag+. Despite increase of RR to 30 microM, however, further inhibition of the Ca2+ efflux was not produced any more (77.8 +/- 12.2% inhibition). A 10 mM caffeine-induced efflux of Ca2+ was blocked slightly by only 0.5 microM RR and almost completely by 3 microM. A slight inhibition (about 28%) of the Ca2+-ATPase activity was observed in the presence of 10 microM Ag+ in 0.5 mg SR protein/ml of medium. RR and caffeine did not affect the enzyme activity. These results indicate that frog SR could induce a rapid release of Ca2+ upon Ag+ and caffeine, suggesting that Ag+ may have two different binding sites to release Ca2+; one is on Ca2+-induced Ca2+ release channel and the other on RR-insensitive site.

Ruthenium red and magnesium ion partially inhibit silver ion-induced release of calcium from sarcoplasmic reticulum of frog skeletal muscles.