Voltage-sensitive calcium channels in a human small-cell lung cancer cell line.
Utilizing the whole-cell patch-clamp method we assessed the Ca2+ current (ICa) in well-established cell lines from human small-cell carcinoma (SCC) of the lung, NCI-H209 and NCI-H187. The Ca2+ current was readily observed in H209 tumour cells (90% of the cells tested), whereas H187 tumour cells only occasionally expressed Ca2+ channels (26% of the cells tested). H209 Ca2+ current was evoked by potentials greater than -30 mV and exhibited partial inactivation over the duration of a 40 ms command potential. This inward current was unchanged by alteration of the holding potential from -80 to -40 mV and the activation phase of the Ca2+ current was best fitted by Hodgkin-Huxley m(t)2 kinetics. H209 Ca2+ current was reduced over 80% by verapamil (100 microM), whereas w-conotoxin (5 microM) appeared to be without effect. In contrast, H209 Ca2+ current was rapidly abolished by nifedipine (10 microM), strongly suggesting the presence of L-type Ca2+ channels. Voltage-gated Ca2+ channels may be important to the secretion of ectopic hormones and the etiology and pathogenesis of Lambert-Eaton syndrome, an autoimmune disorder of the motor nerve terminal in which autoantibodies directed against voltage-gated Ca2+ channels are produced.
Pancrazio
J J
JJ
Department of Biomedical Engineering, University of Virginia Health Sciences Center, Charlottesville 22908.
Oie
H K
HK
Kim
Y I
YI
D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000209:etiology; D008175:Lung Neoplasms / Q000378:metabolism*; D008564:Membrane Potentials; D009543:Nifedipine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D015220:Calcium Channels; D014700:Verapamil; D009543:Nifedipine