Effects of ryanodine on the properties of Ca2+ release from the sarcoplasmic reticulum in skinned skeletal muscle fibres of the frog.

1. We studied the effects of ryanodine on the functions of the sarcoplasmic reticulum (SR) in skinned muscle fibres from Xenopus laevis. 2. Ryanodine treatment decreased the Ca2+ uptake capacity of the SR in a fixed Ca2+ loading condition. The extent of the decrease in the SR Ca2+ uptake capacity was closely correlated with the activity of the Ca(2+)-induced Ca2+ release (CICR) during the ryanodine treatment. This suggests, in agreement with the previous biochemical results, that ryanodine acts on the CICR channels when they are open. 3. The rate of Ca2+ leakage from the SR increased after ryanodine treatment. However, the leakage rate constants were independent of the degree of the loss of SR Ca2+ uptake capacity by the ryanodine treatment. This is inconsistent with the notion that the SR is a single uniform compartment and that the decline in the SR Ca2+ uptake capacity is a result of the increase in the Ca2+ leakage. 4. Partial recovery of the Ca2+ uptake capacity of the ryanodine-treated SR was observed when Ca2+ loading was carried out in the presence of 10 mM procaine. This indicates that procaine partially blocks the open-locked channels. 5. After Ca2+ loading in the presence of procaine, removal of procaine induced a rapid release of Ca2+ from the SR through the open-locked channels. This rapid release was dependent both on the adenine nucleotide concentration and on the Ca2+ concentration. Thus, the 'open-locked' CICR channels are still regulated by Ca2+ and adenine nucleotides.