Column: Bioelectricity within cells holds tantalizing potential for many medical fields

Luigi Galvani discovered bioelectricity in the late 1770s when he began to experiment with the muscular contraction of frog legs by electrical stimulation. He found that he could cause the contraction by touching a frog’s leg with a pair of scissors during a lightning storm, or touching it with a scalpel while a static generator was running.

Later he discovered that he could make the leg twitch without the aid of outside electricity by hanging a frog on a copper hook on an iron wire.

Galvani concluded that animal tissue contained an innate, vital force that was a new form of electricity. Today we understand that it is all one kind of electricity attributable to the charged particles known as electrons and ions.

Today, electrical effects are well known in nerve tissue that controls movement and sensory input to the nervous system. A growing area of cellular bioelectric research studies the effects of electricity on the ion channels of non-neural cells.

There is strong evidence that electric field gradients exist in all developing and regenerating animal tissues as well as surrounding tumors and inflammation sites. Furthermore, researchers now know that bioelectrical communication within cells steers growth and development.

Manipulating cellular electrical signaling might stave off cancer or regenerate limbs if we can crack the bioelectric code.

Developmental biologist Michael Levin and colleagues at Tufts University in 1993 identified patterns of voltages responsible for growing frog eyes. Mimicking this pattern elsewhere created frogs with eyes on their tails or backs. In one case, Levin grew an eye on a tadpole’s gut by adding just one extra ion channel.

Now Levin and others think that bioelectric signals within and between cells contain instructions to initiate stem cells to differentiate into hearts and other organ cells.

Levin has found that only a scant few of hundreds of ion channels on each cell surface dominate voltage gradients within the cell. For example, he discovered that only four ion channels determine on which side of the body organs grow.

Some researchers think it may be possible one day to use bioelectricity to regenerate human limbs. Problems abound, but proof of concept already exists in experiments with reptiles and amphibians that have natural regenerative capability.

Tweaking ion channels has shown promise in cancer treatment and other areas as well. Last year Levin and his colleagues reversed cancerous tumors in frogs using light to manipulate bioelectric signals. Levin says that many cancerous tumors have abnormal bioelectric signaling. Levin says this “wonky” signal indicates massive cell depolarization that allows cancer cells to grow and spread.

In May 2017, Tufts University reported that non-neural tadpole cells, which were depolarized to interfere with the natural electrical signaling, had higher survival rates than control cells when infected with E. coli.

When skin is wounded, a so-called injury current begins immediately. Amputation of newt limbs or digits initiates an even greater injury current in skin cells around the wound. Stumps from accidentally amputated human fingertips, which can regenerate, more often in children, generate a significant injury current as well.

It is apparent that there is a connection between cellular bioelectricity and biochemistry, but there is not yet a magic electric bullet to force regeneration of limbs, cure cancer or boost immune function. Possibilities are encouraging, and a breakthrough could be waiting in some researcher’s lab tomorrow.