O2-sensitive K+ channels in neuroepithelial body-derived small cell carcinoma cells of the human lung

1 Department of Physiology and 2 Institute for Cardiovascular Research, University of Leeds, Leeds LS2 9JT, United Kingdom Neuroepithelial bodies act as airway O 2 sensors, but studies of their activity at the cellular level have been severely limited because they are present at such a low density in lung tissue. Small cell lung carcinoma (SCLC) cells are believed to be derived from neuroepithelial body cells and may represent a model system for investigating the mechanisms of airway chemoreception. Here we have used the whole cell patch-clamp technique to investigate the effects of acute hypoxia on voltage-gated ionic currents and membrane potential in H-146 SCLC cells. Step depolarizations evoked transient inward currents due to activation of Na + and Ca 2+ channels, followed by outward K + currents. K + currents were partially inhibited by 200 µM Cd 2+ (indicative of the presence of a Ca 2+ -dependent component of the K + current) and were inhibited by tetraethylammonium (TEA) in a concentration-dependent manner, although even at 100 mM TEA, a residual K + current could be detected. Hypoxia (P O 2 15-20 mmHg) caused a reversible inhibition of outward K + currents without affecting inward currents. Inhibition by hypoxia was also observed in the presence of Cd 2+ . Hypoxia and TEA caused membrane depolarization in H-146 cells, and their effects appeared additive. These findings indicate that H-146 cells possess O 2 -sensitive, Ca 2+ -independent K + channels that can influence cell membrane potential. SCLC cells may, therefore, represent a good model for investigating the mechanisms underlying O 2 sensing by airway chemoreceptor cells. hypoxia; ion channels; oxygen sensing; airway; chemoreceptor