CALCIUM SIGNALING IN AIRWAY SMOOTH-MUSCLE CELLS IS ALTERED BY IN-VITRO EXPOSURE TO THE ALDEHYDE ACROLEIN

We have previously observed that acrolein administered ex vivo to isol ated airways alters the subsequent airway responsiveness. To examine t he cellular mechanisms involved in this alteration, we have studied th e effect of acrolein exposure on calcium signaling in myocytes freshly isolated from rat trachea. We have also studied the effect of acrolei n exposure on isometric contraction of rat epithelium-free tracheal ri ngs. Tissues were exposed to a variety of acrolein concentrations from 0.1 to 1 mu M and durations front 5 to 15 min. In isolated cells, exp osure to acrolein did not modify the resting cytosolic Ca2+ concentrat ion ([Ca2+](i)) whatever the concentration or duration of exposure, bu t altered the pattern of the Ca2+ response to acetylcholine (ACh). ACh typically induces an initial [Ca2+](i) rise followed by peaks of decr easing amplitude (oscillations). Exposure to a fixed concentration of acrolein (0.2 mu M) for 5 and 10 min significantly enhanced the amplit ude of the initial [Ca2+](i) rise in response to a low concentration o f ACh (0.1 mu M) by 50.8 and 77%, respectively. Similarly, exposure fo r a fixed duration of 10 min significantly enhanced the amplitude of t he initial [Ca2+](i) rise by 49.4% at an acrolein concentration of 0.3 mu M. When cells were stimulated with a high ACh concentration (10 mu M), the value of the first [Ca2+](i) peak was not changed by acrolein exposure, but the frequency at which subsequent peaks occurred was si gnificantly increased by 44.4% after 10 min of exposure to a fixed con centration of 0.2 mu M and by 36.3% following an exposure for a fixed duration of 10 min at the concentration of 0.3 mu M. In contrast, acro lein, whatever the concentration, had no effect on the caffeine-induce d [Ca2+](i) response. In rat epithelium-free tracheal rings, ac rolein increased the response to muscarinic stimulation, with a maximal effe ct observed for an exposure to 0.3 mu M for 10 min. The effect of acro lein on the [Ca2+](i) response of isolated myocytes occurred over a ra nge of doses similar to that on the contractile response of rings, sug gesting that the effect of this pollutant on calcium signaling may acc ount, at least partially, for acrolein-induced airway hyperresponsiven ess.