Bioelectricity and regeneration. I. Initiation of frog limb regeneration by minute currents

Abstract

We have applied 0.2 pamps of current to the forelimb stump of Rana adults for several weeks. The stimulator was designed to avoid introduction of any physiologically active electrode products into the tissue. Current was applied to the dorsal postaxial region of the stump. Cathodal (i.e., distally negative) current initiated partial regeneration; anodal (i.e., distally positive) current initiated extensive destruction of the limb; while implantation of sham stimulators (delivering no current) yielded limbs showing just a healing response. Regeneration was indicated by organized extension of the severed radio-ulna, newly formed muscle, ligament, and isolated cartilage rods that were partially segmented. Moreover, extraordinarily large amounts of nerve developed in the regenerated tissue. We conclude that the cathodally initiated regeneration was mediated by small electrical fields within the stump and not by electrode products. However, a n electrode product (Ag' ion) cannot be completely excluded as a possible mediator of anodal destruction.

Early bioelectric activities mediate redox-modulated regeneration

“…It has been shown that transepithelial potential (TEP)-driven electric current densities (J I ) correlate with and are required for regeneration in amphibians (Borgens et al, 1977b;Jenkins et al, 1996;Nawata, 2001;Reid et al, 2009). Electrical stimulation induces some regeneration in non-permissive adult frog and rat limbs (Becker, 1972;Borgens et al, 1977a;Leppik et al, 2015;Smith, 1967). Moreover, engineered devices (Golding et al, 2016) partially induce mouse digit tip regeneration (Hechavarria et al, 2010) and are in clinical trials to improve paraplegia (Shapiro et al, 2005).…”

The Electrical Response to Injury: Molecular Mechanisms and Wound Healing

“…It was also demonstrated by the same authors that frog limb regeneration could be initiated by driving a small steady current through the stump. 87 The artificial current was driven by a mercury cell battery implanted in the dorsal lymph sac. Current was pulled through the tissue to the mercury cell from the end of the stump through a Ringer's solution-soaked wick (Fig.…”

Ionic Components of Wound Current at Mouse Skin Incisional Wounds

“…Such electric fields are generated when the epithelial layer is disrupted instantaneously and the lesion short-circuits the transepithelial potential difference (2)(3)(4)(5)(6)(7). Electric currents at wounds in human skin (4,(8)(9)(10)(11) and in rodent cornea and skin (5,7,(12)(13) have been measured with various techniques, such as vibrating probes, micro-glass electrodes, micro-needle arrays, and bioelectric imagers (5,12,(14)(15)(16). For example, it is reported that a large outward current of 4 mA cm -2 was measured at the wound edges of rat cornea and human skin.…”