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

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 275; no. 4; p. 709
• Main Authors: O'Kelly, I, Peers, C, Kemp, P. J
• Format: Journal Article
• Language: English
• Published: United States 01.10.1998
• Subjects: Cadmium - pharmacology; Carcinoma, Small Cell - physiopathology; Cell Hypoxia - physiology; Epithelial Cells - physiology; Humans; Ion Channel Gating; Lung Neoplasms - physiopathology; Membrane Potentials - drug effects; Oxygen - metabolism; Potassium Channels - drug effects; Potassium Channels - physiology; Tetraethylammonium - pharmacology; Tetrodotoxin - pharmacology; Tumor Cells, Cultured
• ISSN: 1040-0605; 0002-9513; 1522-1504
• DOI: 10.1152/ajplung.1998.275.4.l709

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