Sodium nitroprusside stimulates ca2+-activated k+ channels in
porcine tracheal smooth muscle cells.
Yamakage, Michiaki, Carol A. Hirshman, and Thomas L. Croxton.
Departments of Anesthesiology & Critical Care Medicine and
Environmental Health Sciences, The Johns Hopkins Medical
Institutions, Baltimore, Maryland 21205
APStracts 2:0189L, 1995.
To directly investigate the possible role of large-conductance Ca2+
-activated K+ (KCa) channels in nitrovasodilator-induced relaxation of
airway smooth muscle we tested the effects of sodium nitroprusside
(SNP) on KCa channels in freshly-dispersed porcine tracheal smooth
muscle cells using cell-attached patch clamp techniques. Channel
open-state probability (nPo) increased 13- fold with exposure to 10-5
M SNP and this was partially reversed by addition of the guanylate
cyclase inhibitors methylene blue (3 [lambda] 10-4 M) or LY-83583 (5
[lambda] 10-5 M). Pretreatment with the cGMP-dependent protein kinase
(G kinase) inhibitor Rp-8-pCPT-cGMPS (2 [lambda] 10-5 M) prevented
activation of KCa channels by SNP. We also tested the ability of G
kinase to directly activate KCa channels in inside-out patches. G
kinase (2.5 U/[mu]l) with ATP (0.5 mM) and cGMP (0.1 mM), but not ATP
and cGMP alone, increased nPo 23-fold. We conclude that SNP activates
KCa channels in airway smooth muscle via guanylate cyclase and G
kinase. Phosphorylation of the channel protein by G kinase may
account for this response. Consequent membrane hyperpolarization and
inhibition of Ca2+ entry through voltage-dependent channels may
contribute to SNP-induced relaxation of airway smooth muscle.
Received 30 May 1995; accepted in final form 21 September 1995.
APS Manuscript Number L170-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95