Cross-linking agents induce rapid calcium release from skeletal muscle sarcoplasmic reticulum.
The passive permeability of skeletal muscle sarcoplasmic reticulum vesicles to Ca2+ ions is drastically increased upon addition of the oxidizing agent cupric phenanthroline. The permeability change, which occurs very rapidly, is partially reversed by reducing agents and cannot be explained by a direct effect of cupric phenanthroline on the lipid moiety of the membranes. The rapid efflux phenomenon is due to protein cross-linking induced by the cupric phenanthroline catalyzed oxidation of SH groups to disulfide bridges. Similar effects are also induced by cross-linking sarcoplasmic reticulum proteins with dithiodipropionic acid disuccinimido ester. The rapid Ca2+ efflux is inhibited by micromolar concentrations of lanthanum and by labeling the Ca2+-ATPase with dicyclohexylcarbodiimide. These observations suggest that Ca2+ channels are formed by chemical modification of the ATPase. The Ca2+ permeability rate of sarcoplasmic reticulum obtained after cross-linking is compatible with the requirements of Ca2+ release in vivo. The possibility that Ca2+-ATPase oligomers might mediate the release process is discussed.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004024:Dicyclohexylcarbodiimide / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology; D008081:Liposomes; D046911:Macromolecular Substances; D009132:Muscles / Q000378:metabolism*; D010618:Phenanthrolines / Q000494:pharmacology; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D013388:Succinimides / Q000494:pharmacology
D003432:Cross-Linking Reagents; D008081:Liposomes; D046911:Macromolecular Substances; D010618:Phenanthrolines; D013388:Succinimides; C014741:bis(1,10-phenanthroline)copper(2+) ion; D004024:Dicyclohexylcarbodiimide; D007811:Lanthanum; D000252:Calcium-Transporting ATPases; C011240:dithiobis(succinimidylpropionate); D002118:Calcium; D004229:Dithiothreitol