Complex formation of skeletal muscle Ca2+-regulatory membrane proteins by halothane.

In skeletal muscle, halothane affects the functions of several Ca2+-regulatory membrane proteins involved in the excitation-contraction-relaxation cycle. To investigate the mechanism by which this volatile anesthetic interferes with Ca2+-homeostasis, we studied potential changes in protein-protein interactions by halothane. Using comparative immunoblotting of microsomal muscle proteins separated on native and denaturing gels, we show here that halothane induces oligomerization of the terminal cisternae Ca2+-binding protein calsequestrin, the junctional ryanodine receptor Ca2+-release channel and the transverse-tubular alpha1-dihydropyridine receptor. This agrees with previous reports on the modulation of Ca2+-release activity by halothane since interactions between the voltage-sensing alpha1-dihydropyridine receptor, the ryanodine receptor and the luminal Ca2+-reservoir might result in a rapid release of Ca2+-ions. Furthermore, this study supports the idea that specific protein sites are involved in the action of inhalational anesthetics and that halothane might trigger abnormal Ca2+-homeostasis in malignant hyperthermia via oligomerization of the mutated ryanodine receptor.