altering the genetic makeup of normally “unexcitable” cells, Duke
Univ. bioengineers have turned them into cells capable of
generating and passing electrical current.
proof-of-concept advance could have broad implications in treating
diseases of the nervous system or the heart, since these tissues rely on
communication between cells to function properly. This communication is
achieved through the passage of electrical impulses, known as action
potentials, from cell to cell.
researchers achieved this transformation by introducing genes into the
cells that form 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.
introducing only three specific ion channels, we were able to give
normally electrically inactive cells the ability to become electrically
excitable,” said Rob Kirkton, a graduate student in the laboratory of
senior investigator Nenad Bursac, associate professor of biomedical
engineering at Duke’s Pratt School of Engineering.
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 Nature Communications.
The researchers are supported by the National Science Foundation, the
American Heart Association, and the National Institutes of Health.
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
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.
three of these ion channels play critical roles in the generation and
propagation of electrical activity in the mammalian heart,” Kirkton
demonstrating that their genetic manipulations made unexcitable human
kidney cells excitable, they tested whether groups of such cells could
carry electrical signals from heart cell to heart cell, both in
two-dimensional and three-dimensional cell culture models.
a key set of experiments, the researchers created an “S”-shaped
pathway, with clusters of normal, living rat heart cells at either end.
The space between the two clusters was filled with a population of
either unexcitable cells (the control), or the genetically engineered
cells. When an electrical stimulus was applied to a heart cell cluster
at one end of the setup, an electrical impulse traveled throughout these
heart cells but immediately stopped and disappeared at the entrance to
the “S”-shaped path containing the unexcitable control cells.
when we used the genetically modified cells, the electrical impulse was
rapidly regenerated and carried throughout the three-centimeter long
pathway, eventually triggering the second cluster of cells to fire on
the other side,” Kirkton said. “Alternatively, if we applied the
stimulus to the modified cells in the center of the pathway, the
electrical impulse travelled outwardly in both directions toward the
heart cells and electrically activated them.”
Duke scientists also said that their engineered excitable cells can be
continuously and easily grown in the lab, are genetically and
functionally identical to each other, and also have the capacity for
further modifications to change their electrical or structural behavior.
cells can be used in the laboratory as a platform for investigating the
roles that specific ion channels have in tissue-level bioelectricity as
well as testing the effectiveness of new drugs or therapies on
bioelectrical activity,” Kirkton said. “They could potentially also be
helpful in the design of new biosensors to detect disease or