Selected contribution: Effect of the aldehyde acrolein on acetylcholine-induced membrane current in airway smooth muscle cells

Acrolein administered to isolated airways has been shown to alter airway re sponsiveness as a consequence of its effect on Ca2+ signaling. To examine t he mechanisms involved, we studied the effect of acrolein on ACh- and caffe ine-induced membrane currents (patch-clamp) in myocytes freshly isolated fr om rat trachea. In cells clamped at -60 mV, ACh (0.1-10 muM) induced a conc entration-dependent inward current, which, in similar to 50% of the cells, was followed by current oscillations in response to high concentration of A Ch (10 muM). Exposure to acrolein (0.2 muM) for 10 min significantly enhanc ed the amplitude of the low-ACh (0.1 muM) concentration-induced initial pea k of current (318.8 +/- 28.3 vs. 251.2 +/- 40.3 pA; n = 25, P < 0.05). At a high-ACh concentration (10 <mu>M), the frequency at which subsequent peaks occurred was significantly increased (13.2 +/- 1.1 vs. 8.7 +/- 2 min(-1); n = 20, P < 0.05). ACh-induced current was identified as a Ca2+-activated C l- current. In contrast, similar exposure to acrolein, which does not alter caffeine-induced Ca2+ release, did not alter caffeine-induced transient me mbrane currents (595 +/- 45 and 640 +/- 45 pA in control cells and in cells exposed to acrolein, respectively; n = 15). It is concluded that acrolein alters ACh-induced current as a consequence of its effect on the cytosolic Ca2+ concentration response and that the protective role of inhibitors of C l- channels in air pollutant-induced airway hyperresponsiveness should be e xamined.