Fig. 2.7. Implanting a small device in the amputation stump of the rat foreleg results in a major
amount of limb regeneration if the device is oriented so that the end of the stump is made negative,
similar to the salamander current of injury. if the device is implanted with the distal end positive there
is no regeneration.
It seemed now abundantly clear that artificially generated electrical currents of appropriate
polarity and magnitude could stimulate regeneration in a variety of animals not normally possessed of
this facility. Nevertheless, the identification of these currents as being the analog of those currents
normally produced by the nervous system was lacking. Growth could be produced by this technique,
but this did not necessarily mean that the neurally related currents measured in animals that were
normally capable of regeneration were the real cause of their regenerative growth. This missing factor
was supplied by one of the latest experiments of Rose (45).
In this experiment he carefully denervated the forelimbs of a number of salamanders, some of
whom received daily applications of negative polarity electrical current to the amputation stump.
Normal complete regeneration occurred in this group and subsequent examination demonstrated no
ingrowth of nerve fibers. The control group demonstrated no regeneration whatsoever. Rose was
therefore able to conclude that the factor supplied by the nerve that is normally responsible for limb
regeneration in the salamander is the flow of an electrical current of the proper polarity and magnitude.
However, the story is not quite over yet as the situation is actually somewhat more complex. However,
it is better understood in the light of our most recent findings.
As early as 1962 Rose had called attention to the importance of a peculiar relationship between
the epidermis and the nerves in the salamander limb regeneration process. The first event in such
regeneration is the overgrowth of the epidermis alone (not the dermis) over the cut end of the
amputation stump. Following this the cut ends of the nerves remaining in the amputation stump begin
to grow into this epidermal "cap" where they form peculiar "synapse-like" junctions with the epidermal
cells. This "neuroepidermal junction" (NEJ) is apparently the primary structure in the regenerative
process, since following its formation the blastema appears, and if the formation of the NEJ is
prevented by interference with either the nerve or the epidermis, or by simply interposing a layer of the
dermis under the epidermis, blastema formation does not occur and regeneration is absent. In
experiments in which limb regeneration was stimulated by electrical means no NEJ formed and we
postulated that its function had been taken over by the applied electrical currents. Therefore, the NEJ
could be postulated to be the single structure that produced the "regeneration type" potentials, not the
nerve, nor the epidermis acting alone.
ELECTROMAGNETISM & LIFE - 35