The Role of Potassium Channels in the Inhibitory Effects ofβ2-adrenoceptor Agonists on DNA Synthesis in Human Cultured Airway Smooth Muscle

Abstract

Opening of calcium-dependent K+channels byβ2-adrenoceptor agonists has been shown to contribute to their smooth muscle relaxant activity. In this study, the influence of K+channel activity on human cultured airway smooth muscle proliferation and on its inhibition by salbutamol have been examined. Studies of86Rb+efflux from the airway smooth muscle cell cultures confirmed that both cromakalim, an activator of ATP-dependent K+channels and salbutamol increased K+channel activity in cultured airway smooth muscle. The efflux of86Rb+was significantly attenuated by non-specific K+channel blockade. Potassium channel blockers had only small and variable effects on [3H]-thymidine incorporation in unstimulated cells and those stimulated with fetal calf serum (FCS) and no effect on FCS-induced increases in cell number. Potassium channel openers also had no substantial inhibitory effects on DNA synthesis or proliferation in cells stimulated with other mitogens including thrombin. Blockade of K+channels had no consistent effects on the inhibition of DNA synthesis and cell proliferation caused by salbutamol (0.3 nm–10μm). The inhibition of DNA synthesis caused by 8 bromoadenosine 3′5′ cyclic monophosphate (1μm–1 mm) or 8 bromoguanosine 3′5′ cyclic monophosphate (1μm–1 mm) was also unaffected by K+channel blockade. These results indicate that changes in K+channel activity have no detectable influence on DNA synthesis and proliferation of human cultured airway smooth muscle cells or on the antiproliferative effects ofβ2-agonists.