Regulation of airway cholinergic neurotransmission by Ca(2+)-activated K+ channel and Na(+)-K+ adenosinetriphosphatase.
Stimulation of Ca(2+)-activated K+ channel and Na(+)-K(+)-ATPase may play an important role in the relaxant responses of airway smooth muscle to certain bronchodilators. To test whether cholinergic neuroeffector transmission can be modulated by Ca(2+)-activated K+ channel and Na(+)-K(+)-ATPase, canine airway smooth muscle was studied under isometric conditions in vitro. Addition of charybdotoxin (10(-7) M) did not alter the contractile responses to acetylcholine but augmented electrical field stimulation-induced contractions at 1-10 Hz (p < .01), whereas apamin and glibenclamide were without effect. This effect of charybdotoxin was dose dependent, with the maximal increase being 36.8 +/- 5.3% (p < .001). Ouabain (10(-7) M) increased contractions induced by both electrical field stimulation and acetylcholine. The magnitude of the increase in 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 Ca(2+)-activated K+ channel and Na(+)-K(+)-ATPase may be operative in the regulation of cholinergic neurotransmission by inhibiting the exocytotic release of acetylcholine from the vagal nerve terminals.
Tagaya
E
E
First Department of Medicine, Tokyo Women's Medical College, Japan.
Tamaoki
J
J
Chiyotani
A
A
Yamawaki
I
I
Takemura
H
H
Konno
K
K
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D001980:Bronchi / Q000294:innervation* / Q000502:physiology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology*; D018999:Charybdotoxin / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018999:Charybdotoxin; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine; D002118:Calcium