Abstract:
BACKGROUND:The authors' purpose of this study was to elucidate the mechanisms of direct effects of halothane on the contractile proteins and Ca2+ release from the sarcoplasmic reticulum Ca2+ stores using isolated skinned strips (sarcolemma permealized with saponin) from rabbit pulmonary arteries. METHODS:The sarcoplasmic reticular Ca2+ stores were examined by immersing the skinned strips sequentially in solutions to load Ca2+ into and release Ca2+ from the sarcoplasmic reticulum using caffeine, inositol 1,4,5-trisphosphate, or halothane. The contractile proteins were assessed by activating the strips with Ca2+ followed by administration of halothane (with or without protein kinase C inhibitors). Tension, fura-2 fluorescence activated by Ca2+ release, and phosphorylation of myosin light chains were measured. RESULTS:Halothane (0.07-3.00%) increased Ca2+, tension, and phosphorylation of myosin light chains in a dose-dependent manner. Halothane decreased accumulation of Ca2+ in the sarcoplasmic reticulum and enhanced the caffeine-induced tension transients. In strips pretreated with caffeine or inositol 1,4,5-trisphosphate, halothane-induced tension transients were reduced but Ca2+ was not. In strips activated by 1 microM Ca2+, halothane (0.5-3.0%) decreased 20-45% of the activated force at 15 min. Halothane (3%) transiently increased the force (20%) associated with increases in Ca2+ and phosphorylation of myosin light chains. The increased force was abolished and the subsequent relaxation was enhanced by the protein kinase C inhibitor bisindolylmaleimide but not by indolocarbazole Gö-6976. CONCLUSIONS:In skinned pulmonary arterial strips, halothane, at clinical concentrations, inhibits uptake of Ca2+ by and induces release of Ca2+ from intracellular stores possibly shared by caffeine and inositol 1,4,5-trisphosphate, which are regulated by phosphorylation of myosin light chains. The time-dependent inhibition of the contractile proteins by halothane may be mediated by Ca2+-independent protein kinase C.
journal_name
Anesthesiologyjournal_title
Anesthesiologyauthors
Su JY,Tang LJdoi
10.1097/00000542-199804000-00031subject
Has Abstractpub_date
1998-04-01 00:00:00pages
1096-106issue
4eissn
0003-3022issn
1528-1175journal_volume
88pub_type
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