[Influence of 4-aminopyridine on voltage-activated K(+) current and cell proliferation in small cell lung cancer]
Liping Wang1, Guoguang Shao, Wenjie Zhang
1Dept. of Thoracic & Cardiovascular Surgery, Second Clinical College, Jilin University, Changchun 130041, China.
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.
Conclusion:
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.
Insights
4-aminopyridine (4-AP) inhibits voltage-activated K(+) channels and reduces cell proliferation in small-cell lung cancer (SCLC). This study demonstrates 4-AP
Area of Science:
- Molecular Biology
- Cell Biology
- Pharmacology
Context:
- Small-cell lung cancer (SCLC) exhibits voltage-activated K(+) channel activity.
- The role of these channels in SCLC proliferation is not fully understood.
- 4-aminopyridine (4-AP) is a known K(+) channel blocker.
Purpose:
- To investigate the inhibitory effects of 4-aminopyridine (4-AP) on voltage-activated K(+) conductance in SCLC cells.
- To determine the impact of 4-AP on SCLC cell proliferation and cell cycle progression.
Summary:
- Whole-cell patch-clamp electrophysiology revealed that 5 mmol/L 4-AP significantly reduced peak outward K(+) current in SCLC cells.
- Flow cytometry analysis demonstrated that 4-AP treatment led to cell cycle arrest at the G(0)/G(1) phase and reduced S and G(2)/M phase populations.
- A concentration- and time-dependent decrease in viable SCLC cells was observed with 4-AP incubation.
Impact:
- Voltage-activated K(+) channels are crucial for SCLC cell proliferation.
- K(+) channel antagonists, such as 4-AP, show potential as therapeutic agents for inhibiting SCLC growth.
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