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Article

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Accepted version

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2019-04-22

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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/147236

Optical Control of Cardiac Function with a Photoswitchable Muscarinic Agonist

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https://doi.org/10.1021/jacs.9b03505

Abstract

Light-triggered reversible modulation of physiological functions offers the promise of enabling on-demand spatiotemporally controlled therapeutic interventions. Optogenetics has been successfully implemented in the heart, but significant barriers to its use in the clinic remain, such as the need for genetic transfection. Herein, we present a method to modulate cardiac function with light through a photoswitchable compound and without genetic manipulation. The molecule, named PAI, was designed by introduction of a photoswitch into the molecular structure of an M2 mAChR agonist. In vitro assays revealed that PAI enables light-dependent activation of M2 mAChRs. To validate the method, we show that PAI photoisomers display different cardiac effects in a mammalian animal model, and demonstrate reversible, real-time photocontrol of cardiac function in translucent wildtype tadpoles. PAI can also effectively activate M2 receptors using two-photon excitation with near-infrared light, which overcomes the scattering and low penetration of short-wave-length illumination, and offers new opportunities for intravital imaging and control of cardiac function.

Subject

Calci, Ones electromagnètiques

Subject (English)

Calcium, Electromagnetic waves

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Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Publicacions de projectes de recerca finançats per la UE

Citation

RIEFOLO, Fabio, et al. Optical Control of Cardiac Function with a Photoswitchable Muscarinic Agonist. Journal of the American Chemical Society. 2019. Vol. 141, num. 18, pags. 7628-7636. [consulted: 9 of August of 2026]. Available at: https://hdl.handle.net/2445/147236

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