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GENERAL ARTICLES

The Effects of Ethanol on Ca²⁺ Sensitivity in Airway Smooth Muscle

Departments of Anesthesiology and Physiology and Biophysics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota

Address correspondence and reprint requests to David O. Warner, MD, Mayo Clinic and Foundation, 200 First St. SW, Rochester, MN 55905. Address e-mail to warner.david{at}mayo.edu

Halothane and other volatile anesthetics relax air-way smooth muscle (ASM) in part by decreasing the amount of force produced for a given intracellular Ca²⁺ concentration (the Ca²⁺ sensitivity) during muscarinic receptor stimulation. To determine whether this is a unique property of the volatile anesthetics, we tested the hypothesis that ethanol, another compound with anesthetic properties, also inhibits calcium sensitization induced by muscarinic stimulation of ASM. A ß-escin permeabilized canine tracheal smooth muscle preparation was used. Ethanol was applied to permeabilized muscles stimulated with calcium in either the absence or presence of acetylcholine. In intact ASM, ethanol produced incomplete relaxation (approxi-mately 40%) at concentrations up to 300 mM. Ethanol significantly increased Ca²⁺ sensitivity both in the presence and the absence of muscarinic receptor stimulation. Although ethanol did not affect regulatory myosin light chain (rMLC) phosphorylation during stimulation with Ca²⁺ alone, it decreased rMLC phosphorylation by Ca²⁺ during muscarinic receptor stimulation. Ethanol, like volatile anesthetics, inhibits increases in rMLC phosphorylation produced by muscarinic receptor stimulation at constant [Ca²⁺]_i. However, despite this inhibition, the net effect of ethanol is to increase Ca²⁺ sensitivity (defined as the force maintained for a given [Ca²⁺]_i) by a mechanism that is independent of changes in rMLC phosphorylation.

Implications: In permeabilized airway smooth muscle, ethanol, like volatile anesthetics, inhibits increases in regulatory protein phosphorylation caused by stimulation of the muscle when intracellular calcium concentration is constant. However, unlike volatile anesthetics, ethanol causes a net increase in force through a process not dependent on protein phosphorylation, an action favoring bronchoconstriction.

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