REGULATION OF AIRWAY CHOLINERGIC NEUROTRANSMISSION BY CA2-ACTIVATED K+ CHANNEL AND NA+-K+ ADENOSINE-TRIPHOSPHATASE()

Stimulation of Ca2+-activated K+ channel and Na+-K+-ATPase may play an important role in the relaxant responses of airway smooth muscle to c ertain bronchodilators. To test whether cholinergic neuroeffector tran smission can be modulated by Ca2+-activated K+ channel and Na+-K+-ATPa se, canine airway smooth muscle was studied under isometric conditions in vitro. Addition. of charybdotoxin (10(-7) M) did not alter the con tractile responses to acetylcholine but augmented electrical field sti mulation-induced contractions at 1-10 Hz (p < .01), whereas apamin and glibenclamide were without effect. This effect of charybdotoxin was d ose dependent, with the maximal increase being 36.8 +/- 5.3% (p < .001 ). Ouabain (10(-7) M) increased contractions induced by both electrica l field stimulation and acetylcholine. The magnitude of the increase i n contractile responses to electrical field stimulation was similar to that of acetylcholine at an ouabain concentration of up to 3 x 10(-7) M, but the former was significantly greater at 10(-6) M ouabain (p < .05). These results suggest that both Ca2+-activated K+ channel and Na +-K+-ATPase may be operative in the regulation of cholinergic neurotra nsmission by inhibiting the exocytotic release of acetylcholine from t he vagal nerve terminals.