The Ca2+ release channel in junctional sarcoplasmic reticulum: gating and blockade by cations.

1. By using a sarcoplasmic reticulum preparation containing feet structures and the 45Ca2+/filtration technique, the opening and closing response of the Ca(2+)-channel was studied. 2. Extravesicular Sr2+ can activate the channel even though this cation is less efficient than Ca2+ in stimulating the Ca2+ release. Higher Sr2+ concentrations display inhibitory action. 3. By studying the closing response high- and low-affinity cations can be distinguished, according to the concentration range required to exert their effect. 4. The synergistic behavior observed by combining high- and low-affinity blocking cations suggest that they interact through the same binding site. 5. The high-and low-affinity cations are noncompetitive blockers of the activating Ca2+ suggesting the existence of an inhibitory site which is different to the activating site.