MUSCARINIC RECEPTOR STIMULATION MODULATES THE EFFECT OF HALOTHANE ON MN2-MUSCLE( INFLUX IN AIRWAY SMOOTH)

Prior studies suggest that the mechanism of action by which halothane relaxes airway smooth muscle depends on the contractile state of the c ell. We hypothesized that halothane would inhibit the influx of Ca2+ i nto canine airway smooth muscle cells during submaximal, but not maxim al, muscarinic stimulation. This hypothesis was tested by using the ra te of quenching of fura 2 fluorescence by Mn2+ in strips of canine tra cheal smooth muscle as an index of Ca2+ influx. Acetylcholine (ACh) pr oduced a dose-dependent increase in Mn2+ influx. Halothane (0.64 +/- 0 .05 mM) significantly decreased Mn2+ influx and intracellular Ca2+ con centration when added to strips stimulated with a submaximal concentra tion of ACh (0.3 mu M) but had no effect on Mn2+ influx or intracellul ar Ca2+ concentration during maximal stimulation with ACh (100 mu M). Similar results were observed when the strips were treated with verapa mil. These results demonstrate that anesthetic effects on Ca2+ homeost asis in intact canine tracheal smooth muscle cells may be critically m odulated by receptor-linked mechanisms.