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Updated: Sep 22, 2025

Advanced Cardiac Rhythm Management by Applying Optogenetic Multi-Site Photostimulation in Murine Hearts
Published on: August 26, 2021
A Photoswitchable Ligand Targeting the β1 -Adrenoceptor Enables Light-Control of the Cardiac Rhythm
Anna Duran-Corbera1, Melissa Faria2, Yuanyuan Ma3
1MCS, Laboratory of Medicinal Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC), CSIC, Jordi Girona, 18, 08034, Barcelona, Spain.
Abstract:
Catecholamine-triggered β-adrenoceptor (β-AR) signaling is essential for the correct functioning of the heart. Although both β1 - and β2 -AR subtypes are expressed in cardiomyocytes, drugs selectively targeting β1 -AR have proven this receptor as the main target for the therapeutic effects of beta blockers in the heart. Here, we report a new strategy for the light-control of β1 -AR activation by means of photoswitchable drugs with a high level of β1 -/β2 -AR selectivity. All reported molecules allow for an efficient real-time optical control of receptor function in vitro. Moreover, using confocal microscopy we demonstrate that the binding of our best hit, pAzo-2, can be reversibly photocontrolled. Strikingly, pAzo-2 also enables a dynamic cardiac rhythm management on living zebrafish larvae using light, thus highlighting the therapeutic and research potential of the developed photoswitches. Overall, this work provides the first proof of precise control of the therapeutic target β1 -AR in native environments using light.
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