ROLE OF INTRACELLULAR CA2-MUSCLE CONTRACTION( STORES IN THE INHIBITORY EFFECT OF HALOTHANE ON AIRWAY SMOOTH)

Background Halothane directly inhibits contraction of airway smooth mu scle, mainly by decreasing the intracellular concentration of free Ca2 + ([Ca2+](i)). The role of intracellular Ca2+ stores, sarcoplasmic ret iculum, is still unclear. We investigated the role of sarcoplasmic ret iculum in the inhibitory effect of halothane on contraction of airway smooth muscle by measuring [Ca2+](i) and intracellular concentration o f inositol 1,4,5-triphosphate ([IP3](i)), a second messenger for relea se of Ca2+ from sarcoplasmic reticulum, Methods: [Ca2+](i) was monitor ed by measuring the 500-nm light emission ratio (F-340/F-380) of a Ca2 + indicator fura-2 with isometric tension of canine tracheal smooth mu scle strip. During Ca2+-free conditions, carbachol (10(-5) M) was intr oduced with pretreatment of halothane (0-3%). During Ca2+-free conditi ons, 20 nM caffeine, a Ca2+-induced Ca2+ release channel opener, was i ntroduced with or without halothane, We measured [IP3](i) during expos ure to carbachol and halothane by radioimmunoassay technique. Results Pretreatment with halothane significantly diminished carbachol-induced increases in [Ca2+](i) by 77% and muscle tension by 83% in a dose-dep endent manner. Simultaneous administration of halothane significantly enhanced caffeine-induced transient increases in [Ca2+](i) and muscle tension in a dose-dependent manner, by 97% and 69%, respectively. Pret reatment with halothane abolished these responses. Rapid increase in [ IP3](i) produced by carbachol was significantly inhibited by 32% by ha lothane in a dose-dependent manner. Conclusions: Halothane, during Ca2 +-free conditions, inhibits transient contraction of airway smooth mus cle induced by muscarinic receptor stimulation, mainly by attenuating the increase in [Ca2+](i). Depletion of Ca2+ from sarcoplasmic reticul um via Ca2+-induced Ca2+ release channels also may contribute to the a ttenuation of the increase in [Ca2+](i) by halothane.