Muscarinic excitation-contraction coupling mechanisms in tracheal and bronchial
smooth muscles.
Janssen, Luke J., Jennifer Wattie, Hwa Lu-Chao, and Tracy Tazzeo.
Asthma Research Group, Firestone Institute for Respiratory Health, St. Joseph's
Hospital, Hamilton L8N 4A6; and the Department of Medicine, McMaster University,
Hamilton, Ontario, Canada L8N 3Z5
APStracts 8:0311A, 2001.
We investigated the mechanisms underlying muscarinic excitation-contraction coupling
in canine airway smooth muscle using organ bath, fura 2 fluorimetric, and patch-clamp
techniques. Cyclopiazonic acid (CPA) augmented the responses to submaximal
muscarinic stimulation in both tracheal (TSM) and bronchial smooth muscles (BSM),
consistent with disruption of the barrier function of the sarcoplasmic reticulum. During
maximal stimulation, however, CPA evoked substantial relaxation in TSM but not BSM.
CPA reversal of carbachol tone persisted in the presence of tetraethylammoium or high
KCl, suggesting that hyperpolarization is not involved; CPA relaxations were absent in
tissues preconstricted with KCl alone or by permeabilization with ß-escin, ruling out a
nonspecific effect on the contractile apparatus. Peak contractions were sensitive to
inhibitors of tyrosine kinase (genistein) or Rho kinase (Y-27632). Sustained responses
were dependent on Ca2+ influx in TSM but not BSM; this influx was sensitive to Ni2+
but not La3+. In conclusion, there are several mechanisms underlying excitation-
contraction coupling in airway smooth muscle, the relative importance of which varies
depending on tissue and degree of stimulation.
Received 29 March 2001; accepted in final form 18 May 2001
APS Manuscript Number A301-1.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 29 June 2001