Linkage between bioelectric signals and cell cycle control via Vmem changes. (A) Schematic illustrating the linkage of membrane potential modulation to ion channel dynamics during the cell cycle. During G1/S transition, the membrane potential becomes hyperpolarized relative to the normal resting potential. Potassium channels from the ATP-sensitive, voltage gated and Ca2+-activated families become active allowing for potassium efflux from the cell; sodium channels also become activated. During the G2/S transition the membrane becomes depolarized, and there is a decrease in potassium channel activity. In addition, G2/M is characterized by the activation of chloride channels and a subsequent efflux of chloride. While the role of potassium channels are the most well-studied in relation to the cell cycle, a number other ion gradients are involved, each contributing to the net membrane potential as described by Goldman-Hodgkin-Katz equation. (B) Membrane voltage in a cell can be altered by a variety of factors, including channel/pump activity in it’s own membrane (cell-autonomous effects), gap junctional communication to neighboring cells of different potential, or nearby electric fields and ion flows from wounded and intact epithelia (the latter two being non-cell-autonomous control mechanisms). In turn, changes in ion flow can be transduced into alterations of the mitotic program by voltage-gated calcium channels and calcium-dependent second-messenger pathways, changes in cell volume, and alterations of transport of mitogens such as serotonin. These can arrive in cells by two voltage-dependent mechanisms: electrophoresis through gap junctions, or changes in the activity of transporters like SERT that are powered by transmembrane potential.