Role of K+ channels in N-acetylprocainamide-induced relaxation of bovine tracheal smooth muscle

We examined the relaxant effects of N-acetylprocainamide, the major hepatic metabolite of procainamide, on bovine tracheal smooth muscle, focusing on the possible involvement of K+ channels. N-acetylprocainamide produced a co ncentration-dependent and full inhibition of the tension development elicit ed by methacholine (0.3 or 1 muM). The potency of N-acetylprocainamide in d iminishing methacholinc-elicited tension development was one-half of that o f procainamide. By comparison, N-acetylprocainamide inhibited high-K+ (40 m M)-induced contraction more potently than procainamide though both inhibiti ons were largely reduced when compared to those against methacholine-induce d contraction. Iberiotoxin (30 nM), Ba2+ (1 mM) or a combination of both ag ents significantly attenuated the relaxant effect of N-acetylprocainamide o n methacholine-induced contraction, whereas apamin (100 nM), 4-aminopyridin e (300 muM), and glibenclamide (10 muM) did not affect it. These results su ggest that N-acetylprocainamide, similar to procainamide, elicits tracheal smooth muscle relaxation mainly through the activation of plasma membrane K + channels. (C) 2001 Elsevier Science B.V. All rights reserved.