Optogenetics, optical imaging combine to stimulate heart muscle by light

Using optogenetics, which uses genetically altered cells to respond to light, and a tandem unit cell (TCU) strategy, researchers at Stony Brook University (Stony Brook, NY) have found a way to control cell excitation and contraction in cardiac muscle cells. The technique, which combines optogenetic stimulation and optical imaging, may help form the basis for a new generation of light-driven cardiac pacemakers and other medical devices.

The research team, led by Emilia Entcheva, Ph.D., associate professor in the Departments of Biomedical Engineering, Physiology & Biophysics, and the Division of Cardiology in Medicine, combined optogenetic stimulation with high-resolution, high-speed optical imaging of electrical activity in heart muscle cells. They are the first research team to use a non-viral optogenetics approach that allows inscription of light sensitivity at the tissue level and results in the lowest light energy ever reported to control electrical activity in excitable tissue.

The team's optogenetic approach offers high spatiotemporal resolution for precise interrogation and control of excitation, seemingly without interfering with essential cardiac properties, according to the study, which was published in the early online edition of Circulation: Arrhythmia & Electrophysiology. Therefore, it presents a new versatile actuation tool in cardiac research for dissection of arrhythmias. Furthermore, cardiac optogenetics based on the TCU strategy may evolve in a more translational direction and lead to a new generation of optical pacemakers and potentially cardioverter/defibrillators.

While electronic cardiac pacemakers and defibrillators are well established and successful technologies, they are not without problems, including the breakage of metal leads, limited battery life, and interference from strong magnetic fields, says Entcheva. Optical stimulation, she says, may eventually offer a new way of controlling heart function.

In the study, the research team used donor cells optimized for light responsiveness (via a light-sensitive protein called channelrhodopsin 2 [ChR2]) and coupled them to heart cells, thus creating light-responsive heart tissue. They found that light-triggered heart muscle contractions were indistinguishable from electrically triggered waves.

The team's technique uses much lower energy and doesn’t require the use of viruses or the introduction of genes from other organisms into heart cells. So cells from a person’s bone marrow or skin can be cultured and modified to respond to light, reducing the possibility that the immune system will reject the light-sensitive cells, according to the study.

Also, in preliminary calculations, the research team estimated that a light-based system might require lower energy for stimulation, which if extrapolated to pacemakers in the future, may potentially translate to life-long batteries.

The team's low-energy light technique could also be useful in creating muscle actuators, testing new drugs for possible cardiac side effects, and potentially improving pacemakers and defibrillators, says Entcheva.

Study funding was provided in part by the Systems Biology Center in New York State, a National Institutes of Health-sponsored program, and by the inter-departmental Institute of Molecular Cardiology and Stony Brook University.


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