AJP - Cell Physiology, Vol 263, Issue 1 C106-C113, Copyright © 1992 by American Physiological Society
Contractile agonists activate voltage-dependent calcium channels in airway smooth muscle cells
M. Tomasic, J. P. Boyle, J. F. Worley 3rd and M. I. Kotlikoff
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6046.
To determine whether agents that cause contraction of airway smooth muscle
affect sarcolemmal calcium channel activity, unitary calcium channel
currents (using Ba2+ as the charge carrier) were recorded in on-cell
configuration from acutely dissociated (dog, pig, and ferret) and cultured
(human) airway smooth muscle cells. Addition of the contractile agonists
methacholine or bradykinin increased the open-state probability of the
large-conductance calcium channel 37.2- and 45-fold, respectively. The
increase in open-state probability was not due to cellular depolarization
because increases occurred in the absence of depolarization. Channel
activation by the agonist was determined to result in the favoring of a
long (16.5 +/- 5.0 ms) open lifetime for the channel, which was not
observed under control conditions, in the absence of BAY K 8644. We also
report the unitary calcium channel currents from a second, smaller
conductance calcium channel. This channel was present in all cell types and
had a mean conductance of 9.5 +/- 0.8 pS (80 mM Ba2+). Exposure of cells to
agonist also resulted in an increase in the open-channel probability of the
small-conductance calcium channel (10.4-fold), which did not result from
cellular depolarization. These experiments demonstrate that the molecular
pathways exist between contractile agonist receptors and sarcolemmal
calcium channels in airway smooth muscle cells. Because membrane patches
were not directly exposed to agonist, receptor-channel linkage probably
occurs via a second messenger-coupling pathway.
