Muscarinic receptor stimulation modulates the effect of halothane on Mn²⁺ influx in airway smooth muscle

Prior studies suggest that the mechanism of action by which halothane relaxes airway smooth muscle depends on the contractile state of the cell. We hypothesized that halothane would inhibit the influx of Ca²⁺ into canine airway smooth muscle cells during submaximal, but not maximal, muscarinic stimulation. This hypothesis was tested by using the rate of quenching of fura 2 fluorescence by Mn²⁺ in strips of canine tracheal smooth muscle as an index of Ca²⁺ influx. Acetylcholine (ACh) produced a dose-dependent increase in Mn²⁺ influx. Halothane (0.64 ± 0.05 mM) significantly decreased Mn²⁺ influx and intracellular Ca²⁺ concentration when added to strips stimulated with a submaximal concentration of ACh (0.3 μM) but had no effect on Mn²⁺ influx or intracellular Ca²⁺ concentration during maximal stimulation with ACh (100 μM). Similar results were observed when the strips were treated with verapamil. These results demonstrate that anesthetic effects on Ca²⁺ homeostasis in intact canine tracheal smooth muscle cells may be critically modulated by receptor-linked mechanisms.