We have previously demonstrated that optogenetic defibrillation can terminate ventricular tachycardia using pain-free illumination (Bruegmann et al, 2016). However, optogenetic technologies require long lasting cardiac gene transfer of light-gated ion channels, which is very challenging. In contrast, photopharmacological methods use photoswitchable compounds that change their conformation upon isomerization by light. Here, we analyzed photopharmacological modulation of cardiac ion channels and initially tested FHU779, a photoswitchable derivative of the L-type Ca2+ channel (LTCC) blocker diltiazem. Patch clamp experiments of adult ventricular cardiomyocytes showed a block of LTCCs when switching FHU779 (25 µM) to the active trans-state by 480 nm illumination compared to a release of block when illuminating with 385 nm to switch FHU779 to the inactive cis-state (20.5±8.8% current switchable, n=12). The spatial precision of light was tested by plating human iPS-derived cardiomyocytes (Cor4U cardiomyocytes, Ncardia) on multi-electrode arrays. In the presence of FHU779 (10µM) local illumination with 480 nm significantly (p=0.016, paired t-test, n=4) shortened field potential durations (170.4±14.8 ms) compared to 385 nm light (186.3±15.9 ms) but only on illuminated electrodes. This indicates a localized shortening of action potential plateaus by photoswitchable LTCC block. Because LTCC are important for sinoatrial pacemaking, the effect of FHU779 on heart rate was tested in explanted Langendorff-perfused hearts. Illumination of the right atrium with 480 nm reduced the heart rate, which was quickly reversed by 380 nm light (5.8±1.8% of heart rate switchable, n=4). Previous optogenetic defibrillation experiments suggested an importance of Na+ channel block for successful defibrillation (Brügmann et al, 2016). We therefore next tested azobenzene trimethylammonium, which was reported to block both Na+ channels, LTCC and excitability in cardiomyocytes (Frolova et al, 2016; Magome et al, 2011). After application of the iodide derivate (AzoTAI, 10 µM) on a monolayer of Cor4U cardiomyocytes, spontaneous beating was reduced by 520 nm illumination (trans-AzoTAI), which could be repetitively restored by 385 nm light (21.3±3.7% of heart rate switchable, n=16). Patch clamp analysis of Cor4U cardiomyocytes showed a 470 nm-induced reduction of Na+ and LTCC currents and a block of spontaneous action potential generation that was reversed by application of 385 nm light (n=3-7). Preliminary experiments on Langendorff-perfused hearts indicate that AzoTAI can block AV-node conduction by 520 nm illumination which is reversed by 385 nm light. Our results demonstrate that photopharmacological methods can be successfully applied in cardiomyocytes and the intact heart to reversibly block ion channel function and may therefore be useful for light-induced termination of cardiac arrhythmia.