Shining light in a heartbeat: Controlling cardiac bioelectricity with membrane-targeted photoswitches

Abstract

The heart's rhythmic contractions are driven by bioelectric signals that coordinate the excitation and propagation of action potentials throughout the cardiac tissue. Maintaining precise control of this rhythm is essential for proper heart function and preventing life-threatening conditions. Traditionally, this regulation has relied on pharmacological interventions, tissue ablation, or electric shock delivery. However, these methods often come with off-target effects, tissue damage, and high energy demands. Optostimulation presents a promising alternative, offering highly precise and minimally invasive control with significantly fewer side effects. In this Perspective, we explore current light-based technologies designed to modulate cardiac bioelectricity, with a particular focus on an innovative approach based on sarcolemma-targeted photoswitches. Finally, we discuss the main translational opportunities and critically examine the key challenges that must be addressed to transition this technology from basic research to clinical application.