Talk about healing energy. Every wound, from the tiniest scratch to the nastiest gash, generates an electric field that pulls in cells that help repair the damage. Now researchers have identified the genes which allow cells to respond to electricity, a finding that could have important medical implications.
Scientists have known for more than 150 years that wounds generate faint electric fields. Most researchers recognize that these fields play some role in wound healing, but just exactly how this worked or which genes were involved in this electric response--called electrotaxis--remained unclear.
Biomedical scientist Min Zhao of the University of Aberdeen in the United Kingdom and colleagues charged at the problem by creating a set of fluorescent markers that lit up when electrical signals set off a biochemical cascade inside the cell. "We saw that the same cascades that control chemotaxis [the response to chemical signals] were also involved in electrotaxis," says team member Josef Penninger of the Institute of Molecular Biotechnology of the Austrian Academy of Sciences. Chemotaxis is also important in wound healing. Although scientists aren't sure exactly how these electrical signaling cascades are activated, they probably cause changes in the internal skeleton of the cell, orienting them towards the electric (or chemical) source, Penninger says.
The next step was figuring out which genes are involved in a cell's electrical response. Applying electric fields to artificial wounds in cell culture dishes and real wounds in rodent corneas, the team detected epithelial cells rushing towards the wound center; reversing the field caused the cells to change direction. Then, the team disrupted a gene called p110 gamma in cultured cells. The gene codes for a chemical, called PI(3)K gamma, which is also a key player in chemotaxis. In mutants without p110 gamma, cells did not move to the wound in response to electric signals. When the researchers disrupted another gene, called PTEN, which down–regulates the levels of PI(3)K gamma in cells, the cells moved 30% faster towards wounds. "This is the first genetic evidence showing that electric fields play a role in guiding cells to heal wounds," says Zhao, whose team publishes its results 27 July in Nature.
"This paper is very solid and well done," says cytokine biologist Michael Levin of the Forsythe Institute in Boston, Massachusetts. The study should encourage people to look more closely at developing therapies using electric fields to stimulate wound healing, adds bioelectrics expert Richard Nuccitelli of The Frank Reidy Research Centre for Bioelectrics in Norfolk, Virginia.