EFFECTS OF CROMOLYN AND NEDOCROMIL ON ION CURRENTS IN CANINE TRACHEALSMOOTH-MUSCLE

Cromolyn and nedocromil are often used in the treatment of asthma, Rec ently, these agents have been shown to block Cl . currents and/or Ca2 currents in a variety of cell preparations. Ca2+ and Cl . currents pl ay central roles in excitation-contraction coupling in airway smooth m uscle. This study therefore aimed to investigate the effects of these agents on membrane currents, elevations of [Ca2+] and contractions evo ked by depolarization and/or acetylcholine in airway smooth muscle, Pa tch-clamp, fura-2 fluorimetric and muscle-bath techniques were used to monitor ion currents, [Ca2+] and contractions, respectively; in canin e tracheal smooth muscle in the presence and absence of the chromones. Cromolyn and nedocromil eliminated voltage-dependent Gaze currents, l eading to a reduction in depolarization-Evoked K+ currents. Both chrom ones had little or no effect on either acetylcholine-evoked release of internal Ca2+ or the subsequent contraction; however, cromolyn (but n ot nedocromil) at high concentrations suppressed Ca2+-dependent Cl . c urrents triggered by acetylcholine. In conclusion, cromolyn and nedocr omil abolished voltage-dependent Ca2+ currents and cromolyn also suppr essed Ca2+-dependent Cl . currents in airway smooth muscle; neither ch romone greatly altered either the release of internally sequestered Ca 2+ or the resultant contractions. Further investigation is needed to d etermine whether the local concentrations obtained by inhaled chromone s within the airway wall allow these cellular effects to occur in pati ents in vivo.