Optogenetic Control of Arrhythmias

Optogenetics offers means to monitor and to modulate cellular function in intact, living cells, with previously unmatched spatiotemporal precision, with the ease of shining light on the study subject. Soon after its introduction in neurobiology, it has rapidly drawn significant interest and evolved quickly to become an important tool in basic cardiovascular research, especially in cardiac electrophysiology. Optogenetics renders the heart responsive to light by the ectopic expression of light-activated ion channels or pumps. The presence of such light-sensitive proteins in the sarcolemma of cardiomyocytes permits the control of the membrane potential by illuminating the heart with a precisely controlled light beam. Brief light pulses generate swift membrane potential deflections that can trigger action potentials (APs), transforming the light source into a cardiac pacemaker. Extended illumination of the light-sensitized myocardium, on the other hand, can keep cardiomyocytes in a refractory state for the duration of the light stimulus and hence can be employed to create reversible conduction block to terminate arrhythmogenic excitation waves. Optogenetics therefore provides means for cardiac pacing and arrhythmia termination by an autogenous mechanism without the application of an external electric field. With gene therapy on the horizon, this might be translated into a clinical application which would offer, for example, shock-free arrhythmia termination for the benefit of diverse patient populations. In this chapter, the basic principles of cardiac optogenetics will be reviewed, as well as key studies exploring the therapeutic potential of this method with a special focus on those carried out in the preclinical context in vivo.