O2-sensitive K+ channels in neuroepithelial body-derived small cell carcinoma cells of the human lung.
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.
O'Kelly
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I
Department of Physiology, University of Leeds, Leeds LS2 9JT, United Kingdom.
Peers
C
C
Kemp
P J
PJ
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
D015221:Potassium Channels; D002104:Cadmium; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D010100:Oxygen