Cross-linking agents induce rapid calcium release from skeletal muscle sarcoplasmic reticulum

Biochemistry. 1984 Aug 14;23(17):3899-907. doi: 10.1021/bi00312a017.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium-Transporting ATPases / metabolism
  • Cell Membrane Permeability / drug effects
  • Cross-Linking Reagents / pharmacology*
  • Dicyclohexylcarbodiimide / pharmacology
  • Dithiothreitol / pharmacology
  • Kinetics
  • Lanthanum / pharmacology
  • Liposomes
  • Macromolecular Substances
  • Muscles / metabolism*
  • Phenanthrolines / pharmacology
  • Rabbits
  • Sarcoplasmic Reticulum / drug effects
  • Sarcoplasmic Reticulum / metabolism*
  • Succinimides / pharmacology


  • Cross-Linking Reagents
  • Liposomes
  • Macromolecular Substances
  • Phenanthrolines
  • Succinimides
  • bis(1,10-phenanthroline)copper(2+) ion
  • Dicyclohexylcarbodiimide
  • Lanthanum
  • Calcium-Transporting ATPases
  • dithiobis(succinimidylpropionate)
  • Calcium
  • Dithiothreitol