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Voltage-activated K+ conductance and cell proliferation in small-cell lung cancer
J J Pancrazio1, I A Tabbara, Y I Kim
1Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville 22908.
Abstract:
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.
Insights
Small-cell lung cancer (SCLC) cells utilize voltage-dependent potassium channels for proliferation. Blocking these channels with 4-aminopyridine (4-AP) or tetraethylammonium inhibits SCLC cell growth, suggesting a therapeutic target.
Area of Science:
- * Electrophysiology
- * Cancer Biology
- * Pharmacology
Background:
- * Small-cell lung cancer (SCLC) is an aggressive malignancy.
- * Voltage-dependent potassium channels are implicated in cellular functions.
- * The role of these channels in SCLC proliferation is not fully understood.
Purpose of the Study:
- * To investigate the expression and function of voltage-dependent potassium channels in SCLC cells.
- * To determine the effect of potassium channel antagonists on SCLC cell viability and proliferation.
Main Methods:
- * Whole-cell patch-clamp recordings were used to measure potassium currents in SCLC cells.
- * SCLC cells were incubated with varying concentrations of 4-aminopyridine (4-AP) and tetraethylammonium.
- * Cell viability and proliferation were assessed over 144 hours.
Main Results:
- * SCLC cells express functional voltage-dependent potassium channels.
- * 4-aminopyridine (4-AP) significantly reduced peak outward potassium current in SCLC cells.
- * Treatment with 4-AP and tetraethylammonium resulted in a concentration- and time-dependent decrease in SCLC cell viability and proliferation.
Conclusions:
- * Voltage-activated potassium channels are present in SCLC cells.
- * Inhibition of these potassium channels suppresses SCLC cell proliferation.
- * Targeting voltage-dependent potassium channels may represent a novel therapeutic strategy for SCLC.