Very low intensity alternating current decreases cell proliferation.

Area of Science:

• Cellular Electrophysiology
• Oncology
• Molecular Biology

Background:

• Electric fields influence cellular functions, including cell cycle regulation and tumorigenesis, via ion channels and membrane integrity.
• Tumor burden can be reduced by electric current through chemical products or heat, but non-thermal effects on cell proliferation are less understood.

Purpose of the Study:

• To investigate the non-thermal effects of low-frequency, low-intensity alternating current (AC) on cell proliferation and survival.
• To identify the ion channels and mechanisms involved in AC-mediated effects on cell proliferation.
• To explore the potential of AC stimulation for cancer treatment, particularly brain tumors.

Main Methods:

• Exposure of normal human cells and various cancer cell lines (brain, prostate, lung) to low-frequency, low-intensity AC.
• Assessment of cell proliferation and survival without thermal influences.
• Investigation of the role of GIRK2 (K(IR)3.2) potassium channels and extracellular potassium concentrations.

Main Results:

• AC stimulation at low frequencies/intensities affected cell proliferation in normal human cells, brain, and prostate neoplasms, but not lung cancer.
• These effects were dependent on GIRK2 (K(IR)3.2) potassium channels and mimicked by increased extracellular potassium.
• Apoptotic cellular changes and cell death were observed only at higher AC frequencies (>75 Hz) or intensities (>8.5 microA).

Conclusions:

• Transmembrane potassium fluxes through inward rectifier channels regulate the cell cycle.
• Low-frequency, low-intensity AC can modulate cell proliferation without significant cell death, suggesting therapeutic potential.
• Existing brain stimulators may be repurposed for treating brain and other tumors by leveraging these electrophysiological effects.