Voltage-activated K+ conductance and cell proliferation in small-cell lung cancer.
Whole-cell patch-clamp measurements indicate that human small-cell lung cancer (SCLC) cells express voltage-dependent potassium channels, whose function is blocked by K+ channel antagonist 4-aminopyridine (4-AP). Exposure of the tumour cells to 4 mM 4-AP reduced the peak outward K+ current (evoked by a depolarization to +80 mV) from 2.05 +/- 0.24 nA (mean +/- SEM, n = 28 cells) to 0.98 +/- 0.12 nA (n = 27). Incubation of SCL cells with 0.1, 4 and 16 mM 4-AP resulted in a concentration- and time-dependent reduction in the number of viable cells when compared with the control; over a period of 144 hours, the drug either significantly reduced the number of viable SCLC cells or caused an apparent cessation of neoplastic cell proliferation, whereas the untreated control cells demonstrated a more than 16-fold multiplication in the number of viable cells. The inhibitory effect on cell growth was also observed with an additional K+ channel antagonist, tetraethylammonium. These data suggest that voltage-activated K+ channels expressed by SCLC cells play a role in neoplastic cell proliferation.
Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville 22908.
J J
JJ
Pancrazio
I A
IA
Tabbara
Y I
YI
Kim
D015761:4-Aminopyridine / Q000494:pharmacology; D018288:Carcinoma, Small Cell; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D015221:Potassium Channels; D015761:4-Aminopyridine