EFFECTS OF K-CHANNEL BLOCKERS ON EPITHELIUM-DERIVED RELAXING FACTOR (EPDRF)-MEDIATED MODULATION OF AIRWAY SMOOTH-MUSCLE CONTRACTILITY()

Airway epithelium plays a role in the regulation of bronchial smooth m uscle tone releasing cyclooxygenase products and epithelium-derived re laxing factor (EpDRF). To test possible involvement of K+ channels in the action of EpDRF, we studied rabbit tracheal segments in the presen ce of indomethacin under isometric conditions in vitro. Mechanical rem oval of the epithelium increased the contractile responses to acetylch oline, so that negative logarithm of the concentration required to pro duce 50% of maximal effect (pD(2)) increased from 5.0 +/- 0.4 to 5.7 /- 0.3 (P < 0.01). Addition of charybdotoxin per se caused a leftward shift of acetylcholine concentration-response curves in epithelium-int act tissues, but the subsequent removal of the epithelium did not furt her potentiated the contractile responses. In contrast, apamin or glib enclamide had no effect on the epithelium-removal-induced potentiation of the contraction. The responses to electrical field stimulation wer e likewise potentiated by epithelial removal, an effect that was aboli shed by charybdotoxin. These results suggest that Ca2+-activated K+ ch annels are involved in the EpDRF modulation of airway smooth muscle re sponsiveness.