Engineering Excitable Cells For Studies of Bioelectricity and Cell Therapy

By altering the genetic makeup of normally "unexcitable" cells, Duke University bioengineers have turned them into cells capable of generating and passing electrical current. This proof-of-concept advance could have broad implications in treating diseases of the nervous system or the heart, since these tissues rely on cells with the ability to communicate with adjacent cells in order to function properly. This communication is achieved through the passage of electrical impulses, known as action potentials, from cell to cell.

The researchers achieved this transformation by introducing genes into the cells that result in the formation of ion channels which are openings, or gates, on the surface of cells. Ion channels allow the flow of electrically charged molecules, or ions, to exit or enter the cell thus enabling the transfer of electric current from one cell to its neighbor.

"By introducing only three specific ion channels, we were able to give normally electrically inactive cells the ability to become electrically excitable," said Rob Kirkton, graduate student in the laboratory of senior investigator Nenad Bursac, associate professor of biomedical engineering at Duke's Pratt School of Engineering.

"We also demonstrated proof-of-concept experiments in which these modified cells were able restore large electrical gaps within and between rat heart cells," Kirkton continued. "This approach to genetically engineering electrical excitability may stimulate the development of new cell or gene-based therapies for excitable tissue repair."

The results of the Duke experiments were published in the journal Nature Communications. The researchers are supported by the National Science Foundation, the American Heart Association and the National Institutes of Health.

"We believe that our approach opens the door to a wide range of novel studies involving electrical communication between cells and may also help us to understand and develop treatments for disorders of electrically active tissues," Bursac said. "For example, genetically engineered excitable cells could be important in treating heart attacks, in which damaged portions of heart muscle become electrically disconnected and are unable to contract in synchrony with neighboring healthy cells."

The Duke researchers hypothesized that a few key ion channels are sufficient to enable cell excitation. They determined that three particular channels could do the job, including those carrying potassium ions, sodium ions, and a gap junction channel, a highly specialized structure that enables cell-to-cell electrical communication.