Biology Reference
In-Depth Information
potential difference across the epithelium in the vicinity of the wound, creating a change in
fields dramatic enough to be monitored even with simple equipment; for this reason, elec-
trical changes associated with wounding were described as early as 1843.
20
Because the body fluids under- and overlying the wounded epithelium are not perfect
conductors, the electrical effect of the breach diminishes with distance and by about
200
m away from a wound the transepithelial potential is within about 5 percent of normal.
If the inside of an epithelium such as the cornea remains at
m
40mV with respect to the
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outside far from the wound site and at
0 mVat the wound site itself, it follows that wound-
ing creates a new electric field between the wound site and 'distant' unaffected cornea,
tangential to the corneal surface (
Figure 10.5
). This new field is complex, in that it is non-
linear and converging on the wound. Critically, from the point of view of a cell at the inner
surface of the epithelium, the new field is orientated so that the wound is effectively a cathode
and the unaffected epithelium an anode. Any cells that undergo cathodally directed galva-
notaxis would therefore be attracted to the wound, and they would receive the signal to
move almost instantly without having to wait for any slow changes in gene expression
caused by chemical signalling from the damaged cells (electric fields travel at the speed of
light).
Healing of damaged rat cornea can be monitored by marking cells fluorescently. One of the
responses seen in normal healing is a vigorous sprouting of processes towards the wound.
Inhibiting the generation of transepithelial electric fields (and consequently, inhibiting the
generation of the tangential wound field that depends on them) with channel blocker
ouabain reduces the amount of sprouting and greatly reduces the accuracy of navigation of
the sprouts that do still form.
7
It also reduces the rate of wound healing. Conversely,
increasing the transepithelial electric field using aminophylline, which enhances efflux
of Cl
, increases the rate of healing.
7
These findings provide circumstantial evidence that
the tangential field really is used for guidance. What is more, the response of cells to the elec-
tric field vector can be so strong that it can override the response to other directional cues.
18
On the other hand, there is evidence from one system that electric fields do not play a critical
regulatory role. Mice heterozygously mutant for Pax6 have corneas that show both low elec-
tric field strengths in wounds, poor cell migration in healing, and poor directional control of
cell migration in electric fields. On the face of it, these facts provide circumstantial evidence
to support the idea that the field controls wounding. However, careful study of the changing
strengths of the field and of cell migration speed during wound healing, in heterozygous and
z
FIGURE 10.5
Wounding swaps the transepithelial electric field for a tangential one.
