Different effects of the K+ channel blockers 4-aminopyridine and charybdotoxin on sensory nerves in guinea-pig lung.

In the isolated guinea-pig bronchus, the potassium channel blocking agent 4-aminopyridine (10(-4) M) caused a contraction which was abolished by capsaicin tachyphylaxis, suggesting involvement of sensory neuropeptides. Charybdotoxin (10(-8), 5 x 10(-8) M), which is a potent blocker of the high-conductance Ca(2+)-activated K+ channel in smooth muscle, caused slowly developing and long lasting bronchoconstriction, which was resistant to capsaicin tachyphylaxis. Neither 4-aminopyridine (10(-3), 10(-4) M) nor charybdotoxin (10(-8), 5 x 10(-8) M) had any significant effect on the bronchoconstriction induced by electrical field stimulation. Furthermore, charybdotoxin had no significant influence on the inhibitory effect of the alpha 2-adrenoceptor agonist SKF 35886 (5 x 10(-7) M) on the bronchoconstriction induced by electrical field stimulation. In the isolated perfused guinea-pig lung, 4-aminopyridine (3 x 10(-5) -10(-3) M) caused bronchoconstriction and enhanced both basal and (at 3 x 10(-5) M) vagal nerve stimulation-evoked calcitonin gene-related peptide outflow from pulmonary sensory nerves. In conclusion, 4-aminopyridine stimulated capsaicin-sensitive sensory neurons and enhanced the sensory activation induced by vagal nerve stimulation in guinea-pig lung. Charybdotoxin, on the other hand, caused bronchial contraction independently of capsaicin-sensitive nerves.