[Influence of 4-aminopyridine on voltage-activated K(+) current and cell proliferation in small cell lung cancer].
OBJECTIVE
To study the inhibition of voltage-activated K(+) conductance and cell proliferation by 4-aminopyridine (4-AP) in the human small-cell lung cancer (SCLC).


METHODS
Inhibition of voltage-activated K(+) current by 4-AP through the whole-cell patch-clamp technique in SCLC cell line was studied. The influence on the cell-cycle by 4-AP was observed by flow cytometry to identify the in vitro inhibition by 4-AP to the cell proliferation of the SCLC cell line.


RESULTS
Exposure of the tumor cells to 5 mmol/L 4-AP reduced the peak outward K(+) current (evoked by a depolarization to +80 mV) from 1.22 +/- 0.11 nA (n = 30) to 0.59 +/- 0.10 nA (n = 28). Flow cytometry results showed that cell population accumulated in the G(0)/G(1) phase and a significantly reduced proportion in the S phase and G(1)/G(2) phase cells after having been exposed to 4-AP for three days. Incubation of the SCLC cells with 0.1, 5, 10, 15, 20 mmol/L 4-AP resulted in a concentration-and time-dependent reduction in the number of viable cells as compared with the control.


CONCLUSIONS
The voltage-activated K(+) channels expressed by SCLC play an important role in SCLC cell proliferation. The proliferation of the SCLC cells is inhibited by K(+) channel antagonists.
Wang
Liping
L
Dept. of Thoracic & Cardiovascular Surgery, Second Clinical College, Jilin University, Changchun 130041, China.
Shao
Guoguang
G
Zhang
Wenjie
W
Guo
Xiping
X
Wang
Chunguang
C
An
Jihong
J
Zhong
Guogan
G
Zhao
Hua
H
D015761:4-Aminopyridine / Q000494:pharmacology*; D018288:Carcinoma, Small Cell / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D015761:4-Aminopyridine