Membrane potential modulates ERK activity and cell proliferation in human cells.

Area of Science:

• Cell Biology
• Biophysics
• Physiology

Background:

• Plasma membrane potential is known to influence cell proliferation in vertebrate cells.
• The precise mechanisms linking membrane potential to proliferation require further elucidation.

Purpose of the Study:

• To experimentally demonstrate the link between membrane depolarization and cell proliferation in human cells.
• To investigate the role of extracellular signal-regulated kinase (ERK) in this process.
• To explore the underlying biophysical mechanisms.

Main Methods:

• Experimental manipulation of plasma membrane potential.
• Measurement of cell proliferation (mitosis).
• Assay of extracellular signal-regulated kinase (ERK) activity.
• Analysis of phosphatidylserine dynamics and calcium influx.

Main Results:

• Membrane depolarization was shown to promote mitosis in human cells.
• ERK activation was found to be voltage-dependent and crucial for depolarization-induced proliferation.
• ERK activity was independent of growth factor stimulation and linked to phosphatidylserine dynamics, not calcium influx.
• Small shifts in resting membrane potential were sufficient to influence proliferative activity.

Conclusions:

• Plasma membrane potential directly regulates cell proliferation in human cells via voltage-dependent ERK activation.
• This mechanism involves altered phosphatidylserine dynamics, independent of calcium.
• The findings expand the known physiological roles of membrane potentials beyond neural systems, highlighting their importance in fundamental cellular processes.