Effect of Halothane on the Oligomerization of the Sarcoplasmic Reticulum Ca2+-ATPase

The exact molecular mechanism of inhalational anesthetics remains obscure. Since the enzyme activity of the sarcoplasmic reticulum Ca2+-ATPase from skeletal muscle fibres is modified by halothane and because protein–protein interactions play an important role in the regulation of Ca2+-regulatory pro...

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Published inBiochemical and biophysical research communications Vol. 271; no. 3; pp. 770 - 776
Main Authors Brennan, Louise K., Froemming, Gabriele R., Ohlendieck, Kay
Format Journal Article
LanguageEnglish
Published Elsevier Inc 19.05.2000
Subjects
Ca2+-ATPase
crosslinking
halothane
inhalathional anesthetics
muscle relaxation
oligomerization
sarcoplasmic reticulum
SERCA
skeletal muscle
succinylcholine
inhalathional anesthetics
oligomerization
halothane
Ca2+-ATPase
succinylcholine
SERCA
skeletal muscle
crosslinking
muscle relaxation
sarcoplasmic reticulum
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Summary:The exact molecular mechanism of inhalational anesthetics remains obscure. Since the enzyme activity of the sarcoplasmic reticulum Ca2+-ATPase from skeletal muscle fibres is modified by halothane and because protein–protein interactions play an important role in the regulation of Ca2+-regulatory proteins, we investigated the effect of this volatile drug on the oligomerization of the fast-twitch Ca2+-ATPase. Using electrophoretic separation following incubation with halothane, increases in relative molecular mass were determined by immunoblotting with a monoclonal antibody to the SERCA1 isoform of the Ca2+-ATPase. Distinct drug-induced decreases in electrophoretic mobility indicated oligomerization of the native Ca2+-pump by halothane, comparable to crosslinking-mediated formation of homo-tetramers. Determination of the effect of halothane on enzyme activity suggested that halothane-mediated protein aggregation triggers a partial inhibition of Ca2+-pump units. Thus, halothane appears to exert its action via specific peptide binding sites and not indirectly by lipid perturbation. These findings support the protein theory of anesthetic action.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2000.2688