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

In skeletal muscle, halothane affects the functions of several Ca2+-regulat ory membrane proteins involved in the excitation-contraction-relaxation cyc le. To investigate the mechanism by which this volatile anesthetic interfer es with Ca2+-homeostasis, we studied potential changes in protein-protein i nteractions by halothane. Using comparative immunoblotting of microsomal mu scle proteins separated on native and denaturing gels, we show here that ha lothane induces oligomerization of the terminal cisternae Ca2+-binding prot ein calsequestrin, the junctional ryanodine receptor Ca2+-release channel a nd the transverse-tubular alpha(1)-dihydropyridine receptor. This agrees wi th previous reports on the modulation of Ca2+-release activity by halothane since interactions between the voltage-sensing alpha(1)-dihydropyridine re ceptor, 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 anes thetics and that halothane might trigger abnormal Ca2+-homeostasis in malig nant hyperthermia via oligomerization of the mutated ryanodine receptor. (C ) 1999 Elsevier Science B.V. All rights reserved.