Cardiac optogenetics: controlling the heart with light

The remarkable capacity of the heart to generate and propagate electrical signals with every heartbeat allows for the regular and synchronous cardiac contraction that keeps us alive. Our ability to modulate the intrinsic rhythm of the heart using external electrical signals has been a fundamental research tool and a life-saving development for many patients with a wide range of heart rhythm conditions. The development of defibrillation, cardioversion and pacemaking have been revolutionary in restoring normal heart rhythm. However, electrical stimulation using physical electrodes is non-specific and has poor spatial resolution. This lack of specificity can result in the painful stimulation of skeletal muscle and sensory neurons in patients with an implantable cardioverter–defibrillator.

Over 40 years ago, Francis Crick envisaged the potential one day to control neurons using light. This report was probably the first description of the field now referred to as optogenetics, a technique that combines genetic and optical approaches to modulate cell excitability with the use of light. The publication by Tobias Brügmann, Philipp Sasse and colleagues in 2010 was the first study to demonstrate optogenetic regulation of the heart, illustrating a powerful technique with potential clinical translation. The capacity of optogenetics to activate neurons had been demonstrated a few years before, and Brügmann and colleagues set out to investigate whether the same technique could offer a novel approach to regulate cardiac excitability. The study used cardiomyocytes that genetically express a light-sensitive ion channel (channelrhodopsin 2), which opens when illuminated with blue light and results in cell membrane depolarization. The investigators showed that short pulses of blue light could stimulate cardiomyocytes in vitro, and the pacemaker region of the cells could be controlled by altering the area of illumination.