Background: Optogenetic defibrillation has been proposed as alternative to electric shocks, which can be harmful. Excitation of ChR2 opsins induces inward current that can defibrillate via depolarization, but this method has feasibility concerns due to light attenuation and high energy needs. GtACR1 opsin has lower energy needs than ChR2 and produces outward current when excited by green light, which hastens repolarization in already-depolarized cells.
Objective: To assess the feasibility reentry termination in computational models of GtACR1-expressing human atria.
Methods: We ran simulations in models derived from 3 late gadolinium enhanced (LGE-)MRI patient scans. Viral delivery of ChR2 or GtACR1 was simulated by incorporating a realistic photocurrent model in 58.2% of cells. Reentry was induced by rapid pacing. Endocardial illumination with blue (ChR2) or green (GtACR1) light was simulated, with realistic transmural attenuation. To analyze termination reliability, we varied pulse timing (70 ms intervals, to span reentrant cycle) and intensity (.001-1 mW/mm²).
Results: In non-illuminated fibrotic atria, arrhythmia was sustained by reentry (Fig A). For most light intensities, ChR2 excitation (Fig B) was less likely to terminate reentry compared to GtACR1 stimulation (Fig C). The mechanism of GtACR1-mediated defibrillation was voltage clamping a large tissue region to near the channel reversal potential of -40 mV (Fig C inset). GtACR1-based termination was reliable for irradiance values as low as 5 µW/mm² (Fig D).
Conclusion: Our findings suggest GtACR1-based optogenetic defibrillation of atrial reentry is feasible, with ~200-fold lower energy requirements than ChR2.