Cardiac optical control of ether-a-go-go-related gene (ERG) using photoactivatable BeKm-1 analogue. A, Left: Schematic of the BeKm-1 uncaging process. Right: hERG (human ether-a-go-go-related gene) current recordings in human embryonic cells (HEK293) illustrating kinetics of current inhibition by incubation with 100 nmol/L noncaged (blue, n=46), caged- (orange, n=94) and uncaged-BeKm-1 (purple, n=180 cells). Average dose-response curves for hERG current inhibition. B, Left: hERG current recordings in control (black), after 100 nmol/L caged-BeKm-1 (orange) and after various illumination times (purple). Middle: Average normalized time course of hERG current before, during, and following light application (n=26 cells). Right: Quantification of current inhibition induced by illumination at steady-state. C, Left: Traces and quantification of action potential duration (APD) at 30%, 70%, and 90% (APD30, APD70, and APD90) repolarization from IK1-clamped human induced pluripotent stem cells (hiPS)-derived cardiomyocytes in control condition (CTL), after perfusion with 200 nmol/L of caged-BeKm-1 (caged) and after illumination (365 nm). Right: Occurrence of early afterdepolarizations ([EADs]; arrows) after BeKm-1 uncaging in hiPS-derived cardiomyocytes and percentages of cells displaying EADs. D, Left: Right atrium-focused illumination area in perfused rat heart. Middle: multielectrode array (MEA) recordings from the right atrium in control (black), after perfusion of 250 nmol/L caged-BeKm-1 (orange) and after uncaging (purple). Right: Quantification of light-induced increase in interbeat interval (IBI). E, Quantification of IBI in zebrafish larvae after injection of 50 µmol/L of caged-BeKm-1 (orange), or after additional 3-min 365-nm (purple) or 2-hours white-light illumination (gray). Quantification of atrio-ventricular (A-V) desynchrony in the same larvae. F, Left: Illustration of the mini-thoracotomy and the illumination of the right atrium (arrow) in anesthetized rat. Middle: Electrocardiograms in control condition, after intravenous injection of 350 µg/kg caged-BeKm-1 (orange), after 10 minutes of illumination (purple) and additional 30 minutes after end of illumination (gray). Right: Quantification of light-induced increase in RR interval in anesthetized rats. Data are presented as mean±SEM, and the number of samples are indicated. Statistical analyses were performed with Prism8 (GraphPad Software Inc.). P values are indicated and obtained by Friedman repeated measure ANOVA with Dunn’s multiple comparison tests (B, C left, and E left), Fisher exact test (C right and E right), and Wilcoxon test (D and F). SR indicates sinus rhythm.