ELECTROMECHANICAL EFFECTS OF ENDOTHELIN ON FERRET BRONCHIAL AND TRACHEAL SMOOTH-MUSCLE

The effects of endothelin (ET) on transmembrane potential and isometric force were studied in ferret bronchial and tracheal smooth muscles. At rest, the muscle cells were electrically and mechanically quiescent. The mean resting potential for the bronchial cells was -70 ± 1 mV (n = 25 cells/8 ferrets), and that of the tracheal cells was -60 ± 1 mV (n = 7 cells/2 ferrets). ET depolarized and contracted both types of muscle cells in a concentration-dependent manner. At 1 nM ET, the bronchial muscle cells were significantly depolarized with concomitant force generation. In contrast, >30 nM ET was required for the tracheal muscle cells to respond. The bronchial cells were further depolarized by 10 and 100 nM ET with electrical slow-wave activity present. The calcium channel antagonist verapamil substantially inhibited the contractions produced by 100 nM ET and abolished the slow-wave activity without affecting the base-line depolarization. Pretreatment of the bronchial muscle with 30 μM indomethacin did not affect the ET-induced contraction. These results suggest that ET modulates airway smooth muscle tone by direct activation and/or depolarization-induced activation of sarcolemmal calcium channels.