title: O2-sensitive K+ channels in neuroepithelial body-derived small cell carcinoma cells of the human lung.
abstract: Neuroepithelial bodies act as airway O2 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 Ca2+ channels, followed by outward K+ currents. K+ currents were partially inhibited by 200 microM Cd2+ (indicative of the presence of a Ca2+-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 (PO2 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 Cd2+. Hypoxia and TEA caused membrane depolarization in H-146 cells, and their effects appeared additive. These findings indicate that H-146 cells possess O2-sensitive, Ca2+-independent K+ channels that can influence cell membrane potential. SCLC cells may, therefore, represent a good model for investigating the mechanisms underlying O2 sensing by airway chemoreceptor cells.
authors.affiliation: Department of Physiology, University of Leeds, Leeds LS2 9JT, United Kingdom.
authors.forename: I
authors.initials: I
authors.lastname: O'Kelly
authors.forename: C
authors.initials: C
authors.lastname: Peers
authors.forename: P J
authors.initials: PJ
authors.lastname: Kemp
mesh_terms: D002104:Cadmium / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000503:physiopathology; D015687:Cell Hypoxia / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating; D008175:Lung Neoplasms / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D015221:Potassium Channels; D002104:Cadmium; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D010100:Oxygen