Role of potassium channels in hypoxic relaxation of porcine bronchi in vitro

Abstract

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.