Figure 1.

Physiology of endogenous bioelectric fields.

(A) Epithelial cells have an asymmetric distribution of ion channels throughout their membrane, which allows them to produce a constitutive ionic current into the tissue. Na⁺/K⁺-ATPases in the basolateral membrane actively transport Na⁺ out of the cell and into the tissue parenchyma (left cell), which depletes intracellular Na⁺ and creates a concentration gradient. Na⁺ channels in the apical domain allow Na⁺ from outside the tissue to diffuse down this newly-established concentration gradient and into the epithelial cell (center cell). Basolateral Na⁺/K⁺-ATPases continue to export sodium (right cell), which creates a net inward Na⁺ current and results in a trans-epithelial Na⁺ concentration gradient. Tight junctions between epithelial cells prevent paracellular diffusion of Na⁺ down its newly-established concentration gradient, and this accumulation of Na⁺ within the tissue creates a trans-epithelial electrical potential (TEP). (B) When the integrity of the epithelium is compromised by injury, large bioelectric fields (EFs) are generated between the lesion site and the surrounding intact tissue through two interrelated electrochemical properties. Large voltage gradients between the injured epithelium where the TEP is grounded (i.e., 0 mV) and the surrounding intact tissue where the TEP is sustained create a static EF, which is a function of a voltage gradient over a distance (E = ΔV/d). Epithelial damage also allows Na⁺ ions to diffuse down their concentration gradient and out of the tissue through a lesion site, and these ionic currents also induce an EF (E = ρI/A where ρ is the resistivity of the tissue, I is the ionic current, and A is the cross-sectional area of the current).