AJP - Lung Cellular and Molecular Physiology, Vol 266, Issue 3 232-L237, Copyright © 1994 by American Physiological Society
Role of potassium channels in hypoxic relaxation of porcine bronchi in vitro
K. S. Lindeman, L. B. Fernandes, T. L. Croxton and C. A. Hirshman
Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland 21205.
To elucidate the mechanism of hypoxic relaxation of airway smooth muscle in
vitro, we investigated the role of adenosine triphosphate-sensitive
potassium (KATP) channels in this response. Second- and third-order porcine
bronchial rings were suspended in 10-ml organ baths containing
Krebs-Henseleit solution. To demonstrate the presence of KATP channels in
this tissue, bronchial rings were contracted with carbachol (1 microM) in
the presence of glibenclamide (100 microM), a KATP channel blocker, or the
vehicle dimethyl sulfoxide (DMSO) (0.1 ml), and dose-response curves to
levcromakalim (a KATP channel opener) or isoproterenol were constructed. In
separate experiments, either glibenclamide or DMSO was added to the chamber
and rings were contracted with carbachol (1 microM) in the presence of 95%
O2-5% CO2. At the plateau, airways were relaxed with either isoproterenol
(0.1 or 0.3 microM) or hypoxia (50, 28, or 0% O2, with constant 5% CO2).
Glibenclamide, when compared with DMSO, shifted the dose-response curve to
levcromakalim, but not to isoproterenol. Glibenclamide attenuated hypoxic
relaxation in rings exposed to 50% O2 (from 35 +/- 4% to 23 +/- 3%, n = 6,
P < 0.001) and increased the time to 63% relaxation in rings exposed to
50% O2 or to 28% O2. Responses in rings exposed to 0% O2 or to
isoproterenol (0.1 or 0.3 microM) were not significantly altered. The
ability of glibenclamide to attenuate the maximum response to 50% O2 and to
increase the time to 63% relaxation during exposure to 50 or 28% O2
suggests that one component of hypoxic bronchodilation during moderate
degrees of hypoxia is opening of KATP channels.
