title: Effects of halothane on the sarcoplasmic reticulum Ca2+ stores and contractile proteins in rabbit pulmonary arteries.
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.
authors.affiliation: Department of Anesthesiology, University of Washington, Seattle 98195-6540, USA. jsu@u.washington.edu
authors.forename: J Y
authors.initials: JY
authors.lastname: Su
authors.forename: L J
authors.initials: LJ
authors.lastname: Tang
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003285:Contractile Proteins / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005456:Fluorescent Dyes / Q000494:pharmacology; D016257:Fura-2 / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology*; D008297:Male; D018994:Myosin Light Chains / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D018685:Anesthetics, Inhalation; D000697:Central Nervous System Stimulants; D003285:Contractile Proteins; D005456:Fluorescent Dyes; D018994:Myosin Light Chains; D002110:Caffeine; D002118:Calcium; D016257:Fura-2; D006221:Halothane