Electrical cues regulate the orientation and frequency of cell division and the rate of wound healing in vivo

Controlling cell division is fundamental. One environmental cue that exerts profound control over both the orientation and frequency of cell division in vivo is a naturally occurring, wound-induced electric field (EF). Wounds in rat corneas generate endogenous EFs in the plane of the epithelial sheet because the transcorneal potential difference (TCPD; +40 mV internally positive) collapses at the wound edge, but is maintained at normal levels at 0.5 mm back from the wound. We manipulated the endogenous EF this creates by using drugs with differing actions. The wound-induced EF controlled the orientation of cell division; most epithelial cells divided with a cleavage plane parallel to the wound edge and perpendicular to the EF vector. Increasing or decreasing the EF pharmacologically, respectively increased or decreased the extent of oriented cell division. In addition, cells closest to the wound edge, where the EF was highest, were oriented most strongly by the EF. Remarkably, an endogenous EF also enhanced the frequency of cell division. This also was regulated by enhancing or suppressing the EF pharmacologically. Because the endogenous EF also regulated the wound healing rate, it may act as one control of the interplay between cell migration and cell division during healing.