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Title: Optical Control of Cardiac Function with a Photoswitchable Muscarinic Agonist
Author: Riefolo, Fabio
Matera, Carlo
Garrido Charles, Aida
Gomila Juaneda, Alexandre
Sortino, Rosalba
Agnetta, Luca
Claro Izaguirre, Enrique
Masgrau, Roser
Holzgrabe, Ulrike
Batlle, Montserrat
Decker, Michael
Guasch i Casany, Eduard
Gorostiza Langa, Pablo Ignacio
Keywords: Calci
Ones electromagnètiques
Electromagnetic waves
Issue Date: 22-Apr-2019
Publisher: ACS Publications
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.
Note: Versió postprint del document publicat a:
It is part of: Journal of the American Chemical Society, 2019, vol. 141, num. 18, p. 7628-7636
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Appears in Collections: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

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