The effects of ethanol on Ga2+ sensitivity in airway smooth muscle

Halothane and other volatile anesthetics relax airway smooth muscle (ASM) i n part by decreasing the amount of force produced for a given intracellular Ca2+ concentration (the Ca2+ sensitivity) during muscarinic receptor stimu lation. To determine whether this is a unique property of the volatile anes thetics, we tested the hypothesis that ethanol, another compound with anest hetic properties, also inhibits calcium sensitization induced by muscarinic stimulation of ASM. A beta -escin permeabilized canine tracheal smooth mus cle preparation was used. Ethanol was applied to permeabilized muscles stim ulated with calcium in either the absence or presence of acetylcholine. In intact ASM, ethanol produced incomplete relaxation (approximately 40%) at c oncentrations up to 300 mM. Ethanol significantly increased Ca2+ sensitivit y both in the presence and the absence of muscarinic receptor stimulation. Although ethanol did not affect regulatory myosin light chain (rMLC) phosph orylation during stimulation with Ca2+ alone, it decreased rMLC phosphoryla tion by Ca2+ during muscarinic receptor stimulation. Ethanol, like volatile anesthetics, inhibits increases in rMLC phosphorylation produced by muscar inic receptor stimulation at constant [Ca2+](i). However, despite this inhi bition, 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 indep endent of changes in rMLC phosphorylation.