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.
"All three of these ion channels play critical roles in the generation and propagation of electrical activity in the mammalian heart," Kirkton explained.
After 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.
In 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.
"However, 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 th
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