ABSTRACT

The evidence that electrical šelds exist within extracellular tissue spaces is strong and wide ranging across animal and plant kingdoms (Jaffe, 1985). Demonstrating unequivocal roles for these electrical signals in regulating cellular physiology has been challenging, and many biologists are not convinced that they have physiological or pathological relevance. Three issues probably explain this:

Introduction ....................................................................................................... 121 Electrical Gradients in Developing and Regenerating Epithelia ....................... 123 Skin and Cornea Separate Charge, Which Creates a Transepithelial Potential (TEP) Difference ................................................................................ 125 Epithelial Cells Respond Strongly to an EF ..................................................... 127 Corneal Wound Healing in Rat Is Regulated by the Wound-Induced EF ......... 130 The Wound-Induced EF Regulates Proliferation of Epithelial Cells In Vivo .... 130 The Wound-Induced EF Regulates the Axis of Epithelial Cell Division In Vivo ................................................................................................................131 The Wound-Induced EF Regulates Nerve Sprouting In Vivo ............................ 132 Current Epithelial Wound Healing Treatments Unwittingly Target the Endogenous EF ................................................................................................. 133 Electrical Wound Healing ................................................................................. 133 References ......................................................................................................... 134

1. Technological advances. Using string galvanometer meas ure ments and extracellular recording electrodes, much was discovered in the šrst half of the 1900s of the dynamic, extracellular electrical events that regulate the heartbeat, that arise from the conduction of a compound action potential in peripheral nerves, and that are generated during epileptic seizures, or during cortical spreading depression in the brain. With the development of the intracellular microelectrode, attention shifted to electrical events across a single cell membrane rather than in the extracellular spaces, and the patch clamp technique brought further reductionist concentration on single-channel conductance events within a cell membrane. This had a profound effect in refocussing interest on a different scale (single ion movements rather than the collective effects of many depolarizing axons), on a different location (across a lipid bilayer rather than through the extracellular spaces), and on a different time frame (milliseconds rather than minutes to hours). Consequently, much of the work of our illustrious forebears, in carefully describing the extracellular electrical signatures in a variety of tissues, is unknown.