In Silico Optogenetic Control of Spiral Waves in GtACR1-transduced Atrial Diffuse and Focal Fibrotic Tissues

Atrial fibrosis is a significant factor in inducing atrial fibrillation (AF). In recent years, optogenetics has been experimentally confirmed to effectively terminate AF in rodents, whereas its effectiveness in human AF cardioversion has not yet been clearly established due to considerations of experimental safety and technological challenges. As an important adjunct and complement to clinical experimental research, computational modeling can provide both phenomenological simulation and mechanistic explanation for the occurrence and progression of AF. This study employed GtACR1transduced human atrial cells and two-dimensional models of human atrium with focal fibrosis and diffusefibrosis in chronic AF, to investigate the effects of subthreshold illumination on cellular electrophysiology and spiral wave dynamics.Our results showed that with the same proportion of atrial fibrosis and gap-junctional conductance, the transmembrane potential of atrial myocytes was compelled to align with the reversal potential of GtACR1 in sub-threshold illumination.This "optogenetic voltage forcing" phenomenon effectively thwarted the re-excitation of atrial myocytes.As a result, spiral waves were terminated in both pure atrial muscle and tissues exhibiting diffuse and focal atrial fibrosis.