Electrical stimulation of the heart is a common phenomenon. If you are CPR/AED certified, you’ve practiced saving someone’s life using a defibrillator. If you know anyone with a heart problem, chances are they have a pacemaker or have talked to their doctor about getting one. Both defibrillators and electrodes use direct electrical stimulation to correct cardiac arrhythmias.
While this technology can be life saving, it shocks the heart with a great amount of force. This force is often non-specific, shocking the entire heart at once, and can cause pain or tissue damage.
Five biomedical engineers from Johns Hopkins and Stony Brook University are looking into an enlightening technology that can mitigate these problems: optogenetics. Already successfully used in brain tissue, optogenetics takes advantage of light-sensitive proteins called opsins.
Tissues modified to express opsins will elicit bioelectric responses in the presence of optical illumination. Unlike direct electrical stimulation, which operates through Faradaic charge transfer, optical illumination via opsins involves a transmembrane current. The change in transduction mechanisms widens the range of safe pulse widths and amplitudes. This means that stimulation via light can be more finely tuned than stimulation by electricity.
Furthermore, the overall energy needed for the stimulated cell to reach an action potential is less for light-stimulation than electrical stimulation. Less energy means less of a chance of tissue damage. The BME team at Hopkins, led by Natalia Trayanova, the Murray B. Sachs Professor of Biomedical Engineering, has developed a cardiac electrophysiology and electromechanics model of heart optogenetics. By using biological data from Emilia Entcheva’s lab at Stony Brook, Trayanova’s lab is tweaking the precision and accuracy of their model so it better approximates various levels of structural hierarchy in the heart. They have developed a framework that models the heart from molecular interactions to the organ level.
In their Aug. 28 paper published in Nature Communications, the Hopkins and Stony Brook researchers discussed different optogenetic-based xperiments performed with their heart model. Based on these tests, the researchers have shown that donor cells are more efficient providers of illumination than viral transfection and that opsin-expressing cells show increased excitability in Purkinje fibers as compared to ventricular cells.
Furthermore, a low density and high patchiness of opsin-rich cells was shown to be associated with a lower energy needed for action potential stimulation. This means that light can more efficiently stimulate the heart when the opsin-rich cells are sprinkled throughout the tissue. The researchers think this is because patchiness maximizes the interface between electrical sources (i.e. donor cells) and sinks (myocytes at rest). This again supports the idea that donor cells should be used, as they lend themselves to patchiness better than viral transfection methods.
While the Hopkins and Stony Brook researchers understand that there are limits to their findings, as they cannot replace in vitro or in vivo studies, they have great hope for the possibilities of their heart model. It can help other researchers further probe the potential of optogenetics to replace current electrical stimulation models.
In fact, this newly developed model may be better than other research systems because it allows for testing and understanding at various levels of structural hierarchy. This model may become a catalyst for a field of cardiac optogenetics. The market is ripe for new discoveries, as heart disorders and diseases are comfortably staking their ground in the United States.
