Calcium Release from Isolated Sarcoplasmic Reticulum Due to 4,4′-Dithiodipyridine1

Abstract

The effects of SH reagents on Ca²⁺ release from sarcoplasmic reticulum (SR) vesicles were examined by the tracer method using ⁴⁵Ca²⁺. Among the various SH reagents tested, 4,4′-dithiodipyridine (PDS) was found to induce Ca²⁺ release most specifically from the heavy fraction of SR vesicles. Further, the following results were obtained. (i) PDS bound covalently to proteins in the SR membrane and induced Ca²⁺ release. (ii) The Ca²⁺ release was further enhanced by ATP and caffeine, but inhibited by procaine, ruthenium red and various divalent cations. (iii) PDS enhanced the Ca²⁺ release in the whole range of Ca²⁺ concentrations tested. (iv) Choline permeability was also enhanced by PDS. Further, the electrical conductance of the Ca²⁺-induced Ca²⁺ release channels was studied by incorporating them into lipid bilayers and it was found that PDS increased the probability of opening of the channels. These results suggest that PDS binds to certain SH groups of the Ca²⁺ induced Ca²⁺ release channels in the SR membrane and thus induces Ca²⁺ release.