Effects of intravenous anesthetics on Ca²⁺ sensitivity in canine tracheal smooth muscle

Background: Halothane and other volatile anesthetics relax airway smooth muscle in part by decreasing the amount of force produced for a particular intracellular calcium concentration (the Ca²⁺ sensitivity) during muscarinic receptor stimulation. In this study, ketamine, propofol, and midazolam were evaluated to determine whether the inhibitory effect of volatile anesthetics on this signal transduction pathway is a general property of other types of anesthetic drugs. Methods: A β-escin permeabilized canine tracheal smooth muscle preparation was used. Ketamine, propofol, and midazolam, in concentrations producing near-maximal relaxation in intact airway smooth muscle (200 μM, 270 μM, and 100 μM, respectively), were applied to permeabilized muscles stimulated with calcium in either the absence or the presence of muscarinic receptor stimulation provided by acetylcholine. The effect of halothane also was evaluated. Results: Confirming previous studies, halothane (0.75 mM) decreased calcium sensitivity during muscarinic receptor stimulation. None of the intravenous anesthetics studied affected Ca²⁺ sensitivity, either in the absence or the presence of muscarinic receptor stimulation. Conclusions: Intravenous anesthetics in high concentrations directly relax canine tracheal smooth muscle without affecting Ca²⁺ sensitivity. The inhibition of agonist- induced increases in Ca²⁺ sensitivity of canine tracheal smooth is not a common property of anesthetics, but is unique to volatile agents.