Membrane potential modulates ERK activity and cell proliferation

The plasma membrane potential has been linked to cell proliferation for more than 40 years. Here we experimentally showed that membrane depolarization upregulates cell mitosis, and that this process is dependent on voltage-dependent activation of ERK. ERK activity exhibits a membrane potential-dependency that is independent from the growth factor. This membrane potential dependence was observed even close to the resting membrane potential, indicating that small changes in resting membrane potential can alter cell proliferative activity. The voltage-dependent ERK activity is derived from changed dynamics of phosphatidylserine which is present in the plasma membrane and not by extracellular calcium entry. The data suggests that crucial biological processes such as cell proliferation are regulated by the physicochemical properties of the lipid. This study suggests that membrane potential may have diverse physiological functions beyond the action potential, which is well-established in the neural system.