Objective: To investigate the mechanisms that keratinocytes use to sense and respond to electrical guidance cues that direct their migration into the wound bed. A lateral electric field (EF) is generated immediately upon wounding skin. Endogenous EFs play an important role in embryonic development and wound repair. They are the first guidance signal that wound cells will receive to indicate damage has occurred and stimulate the physiological responses required for the wound to heal. Indeed the center of the wound becomes the cathode of the endogenous EF, measured to be between 100-150mV/mm. Methods: Keratinocytes migrate directionally towards the cathode of an applied physiological EF in vitro, a process known as galvanotaxis. We can monitor migration using a customised inverted microscope system to allow live imaging of cell migration in the presence and absence of applied EF and treatments. Results: We have used a range of purinergic agonists, antagonists, hemichannel blockers and membrane potential fluorescent indicators to determine their effect on keratinocyte migration and galvanotaxis. Here we report that purinergic receptors and pannexin and connexin hemichannels play an important role in the ability of keratinocytes to sense and respond to EFs. Conclusion: Localised changes in membrane potential could initiate the polarised opening of hemichannels, releasing ATP and initiating polarised downstream purinergic receptor signaling that we have discovered is essential for keratinocyte galvanotaxis. Future research will further delineate the timing of events, the downstream signaling mechanisms and reveal the EF sensor for keratinocytes.