High-affinity Ca²⁺-binding site inhibiting Ca²⁺ release from sarcoplasmic reticulum

Ca²⁺ release from sarcoplasmic reticulum membranes, activated by alkaline pH occurs only when EGTA is present in the release medium. Addition of very low concentrations of Ca²⁺ to the medium inhibits Ca²⁺ release. The concentration of free Ca²⁺ required for 50% inhibition ranges from between 5 and 20 nM in different experiments and/or membrane preparations, irrespective of whether the free Ca²⁺ concentration is controlled by EGTA or CDTA. Other divalent cations such as Mn²⁺, Ba²⁺, Cu²⁺, Cd²⁺ and Mg²⁺ also exert an inhibitory effect on Ca²⁺ release, with higher or lower potency than that of Ca²⁺. The inactivation of Ca²⁺ release by Ca²⁺ is reversible. We suggest the involvement of high-affinity Ca²⁺-binding sites in the control of Ca²⁺ release.