Acetylcholine and caffeine activate cl and suppress k+ conductances
in human bronchial smooth muscle.
Janssen, Luke J.
Department of Medicine, McMaster University, Hamilton, Ontario,
Canada L8N 3Z5
APStracts 2:0224L, 1995.
The conductance changes underlying agonist-evoked depolarization in
human airway smooth muscle (ASM) were examined using single ASM cells
liberated enzymatically from non-carcinomatous bronchi and studied
using patch-clamp techniques. Step commands to potentials at or more
positive than the resting membrane potential evoked outward current,
which was predominantly delayed rectifier K+ current with some Ca2+
-dependent K+ current. Caffeine (5 mM) evoked depolarization and
contraction lasting several minutes. During voltage clamp at -60 mV,
caffeine evoked inward current with a latency of nearly equal to 1 s,
mean amplitude of 320+/-65 pA, and a duration of nearly equal to 5 s
(even though agonist application exceeded this duration). Using the
perforated-patch configuration, these responses could be evoked
repeatedly at 4 minute intervals for up to 30 minutes; rupture of the
membrane and dialysis of the cytosol, however, abrogated the
responses to caffeine. The current was outwardly rectifying with mean
reversal potential (Vrev) of -31+/-4 mV. When K+ conductances were
blocked by Cs+, the current-voltage relationship was linear (i.e. an
outwardly-rectifying component was eliminated) and Vrev was displaced
in the positive direction to +2+/-1 mV. Changes in the Cl_
equilibrium potential were accompanied by a displacement of Vrev in a
manner predicted by the Nernst equation for a Cl_ current. The
effects of caffeine were mimicked by acetylcholine; in addition,
acetylcholine and caffeine each occluded the response to the other
agonist. Spasmogens also caused a prolonged suppression of K+
currents (both Ca2+-dependent and delayed rectifier). We conclude
that, in human ASM, acetylcholine and caffeine cause a transient
activation of Ca2+-dependent Cl_ current (due to release of internal
Ca2+) and prolonged suppression of K+ currents, leading to
depolarization and contraction.
Received 6 April 1995; accepted in final form 4 December 1995.
APS Manuscript Number L108-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 12 December 95