Electrical signals play an integral role in the function of many of our organ systems and are routinely used in the diagnosis of disease in the heart and nervous system. Our largest organ, the skin, generates a voltage across itself everywhere on the body, yet the signaling function of this “skin battery” remains largely unexplored.
This skin battery will drive an ionic current out through any wound where the resistance is low and as this “wound current” flows out of the wound it will in turn generate an electric field within the skin along the lines of current flow. Dubois–Reymond first discovered that ionic currents exit skin wounds 165 years ago using a galvanometer.1
This was confirmed by Illingworth and Barker2
using the more modern vibrating probe technique.3,4
They measured up to 10 μA/cm2
exiting accidentally amputated fingertips in children during a 2-week period following the injury. This wound current flows through the tissue which has a certain resistivity so this flow must generate an electric field in the skin bordering the wound. While this electric field has not yet been measured in humans, it has been measured in the skin of guinea pigs, newts, and salamanders (reviewed in5
). The lack of human studies is due, in part, to the difficulty of carrying out recordings in human wounds using the standard microelectrode technology. We have developed a new approach, the bioelectric field imager (BFI), which does not require any electrode contact at the wound site so it makes possible the noninvasive measurement of the electric fields near mammalian wounds. Using this new tool we have revealed for the first time the electric field pattern surrounding skin wounds in mice and humans. The significance of the BFI is that it enables us to visualize the electric field lines associated with wounds noninvasively.
This electric field is the first signal generated upon wounding and it initiates the wound healing process by triggering the active migration of keratinocytes and other cell types toward the wounded region by galvanotaxis.6
The ultimate driving force for all wound currents is the voltage across the epidermis. The epidermis of the skin normally generates a voltage across itself, termed the transepidermal potential (TEP), by pumping positive ions from its apical to its basal side and Cl–
from its basal to apical side. This is accomplished by segregating Na+
channels to the apical end and K+ channels to the basal end of the epithelial cells, while utilizing a Na+
-ATPase to lower intracellular [Na+
] and raise intracellular [K+
] (). This low intracellular [Na+
] (combined with the negative membrane potential) results in Na+
movement into the cell on the apical end where the channels are localized, and the high intracellular [K+
] results in K+
efflux on the basal side where the K+
channels are localized. This transepidermal ion flux creates a TEP of between 20–50 mV, inside positive, in mammalian skin,7,8
and has been termed the “skin battery”9
(). After wounding, this TEP will drive current out the low resistance pathway created by the wound (). In intact skin, current flow is limited by the very high resistance of the stratum corneum and the tight junctions between cells that form the monolayers in the epidermis. Because this positive wound current flows toward the wound on the basal side of the epidermis, and then away from the wound on the apical side, a lateral electric field will be generated by this flow of wound current on both sides of the epidermis but will exhibit opposite polarities on the two sides (). This model predicts that the field just beneath the stratum corneum will be oriented with the positive pole at the wound and the negative pole away from the wound, and this field has indeed been measured in guinea pig skin to be about 100 mV/mm.7
Our preliminary measurements on human skin wounds have also detected fields of this polarity and amplitude. In contrast to this, the field deeper in the epidermal multilayer will have the opposite polarity, with the negative pole at the wound site ().
Figure 1 Generation of skin wound electric fields. (A) Diagram of a typical epithelial cell in a monolayer with Na+ and Cl– channels localized on the apical plasma membrane and K+ channels localized on the basolateral membranes along with the Na+/K+-ATPase. (more ...)