Role of stretch-activated channels in light-generated action potentials mediated by an intramembrane molecular photoswitch

Abstract Background The use of light to control the activity of living cells is a promising approach in cardiac research due to its unparalleled spatio-temporal selectivity and minimal invasiveness. Ziapin2, a newly synthesized azobenzene compound, has recently been reported as an efficient tool for...

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Main Authors: Chiara Florindi, Vito Vurro, Paola Moretti, Chiara Bertarelli, Antonio Zaza, Guglielmo Lanzani, Francesco Lodola
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Journal of Translational Medicine
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Online Access:https://doi.org/10.1186/s12967-024-05902-4
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author Chiara Florindi
Vito Vurro
Paola Moretti
Chiara Bertarelli
Antonio Zaza
Guglielmo Lanzani
Francesco Lodola
author_facet Chiara Florindi
Vito Vurro
Paola Moretti
Chiara Bertarelli
Antonio Zaza
Guglielmo Lanzani
Francesco Lodola
author_sort Chiara Florindi
collection DOAJ
description Abstract Background The use of light to control the activity of living cells is a promising approach in cardiac research due to its unparalleled spatio-temporal selectivity and minimal invasiveness. Ziapin2, a newly synthesized azobenzene compound, has recently been reported as an efficient tool for light-driven modulation of excitation-contraction coupling (ECC) in human-induced pluripotent stem cells–derived cardiomyocytes. However, the exact biophysical mechanism of this process remains incompletely understood. Methods To address this, we performed a detailed electrophysiological characterization in a more mature cardiac model, specifically adult mouse ventricular myocytes (AMVMs). Results Our in vitro results demonstrate that Ziapin2 can photomodulate cardiac ECC in mature AMVMs without affecting the main transporters and receptors located within the sarcolemma. We established a connection between Ziapin2-induced membrane thickness modulation and light-generated action potentials by showcasing the pivotal role of stretch-activated channels (SACs). Notably, our experimental findings, through pharmacological blockade, suggest that non-selective SACs might serve as the biological culprit responsible for the effect. Conclusions Taken together, these findings elucidate the intricacies of Ziapin2-mediated photostimulation mechanism and open new perspectives for its application in cardiac research.
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institution Kabale University
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spelling doaj-art-df3124a47a35433495c4e2113205fc322024-12-01T12:42:18ZengBMCJournal of Translational Medicine1479-58762024-11-0122111210.1186/s12967-024-05902-4Role of stretch-activated channels in light-generated action potentials mediated by an intramembrane molecular photoswitchChiara Florindi0Vito Vurro1Paola Moretti2Chiara Bertarelli3Antonio Zaza4Guglielmo Lanzani5Francesco Lodola6Department of Biotechnology and Biosciences, University of Milano-BicoccaCenter for Nano Science and Technology, Istituto Italiano di TecnologiaCenter for Nano Science and Technology, Istituto Italiano di TecnologiaCenter for Nano Science and Technology, Istituto Italiano di TecnologiaDepartment of Biotechnology and Biosciences, University of Milano-BicoccaCenter for Nano Science and Technology, Istituto Italiano di TecnologiaDepartment of Biotechnology and Biosciences, University of Milano-BicoccaAbstract Background The use of light to control the activity of living cells is a promising approach in cardiac research due to its unparalleled spatio-temporal selectivity and minimal invasiveness. Ziapin2, a newly synthesized azobenzene compound, has recently been reported as an efficient tool for light-driven modulation of excitation-contraction coupling (ECC) in human-induced pluripotent stem cells–derived cardiomyocytes. However, the exact biophysical mechanism of this process remains incompletely understood. Methods To address this, we performed a detailed electrophysiological characterization in a more mature cardiac model, specifically adult mouse ventricular myocytes (AMVMs). Results Our in vitro results demonstrate that Ziapin2 can photomodulate cardiac ECC in mature AMVMs without affecting the main transporters and receptors located within the sarcolemma. We established a connection between Ziapin2-induced membrane thickness modulation and light-generated action potentials by showcasing the pivotal role of stretch-activated channels (SACs). Notably, our experimental findings, through pharmacological blockade, suggest that non-selective SACs might serve as the biological culprit responsible for the effect. Conclusions Taken together, these findings elucidate the intricacies of Ziapin2-mediated photostimulation mechanism and open new perspectives for its application in cardiac research.https://doi.org/10.1186/s12967-024-05902-4Light stimulationMolecular photoswitchesCardiac cell modulationStretch-activated channels
spellingShingle Chiara Florindi
Vito Vurro
Paola Moretti
Chiara Bertarelli
Antonio Zaza
Guglielmo Lanzani
Francesco Lodola
Role of stretch-activated channels in light-generated action potentials mediated by an intramembrane molecular photoswitch
Journal of Translational Medicine
Light stimulation
Molecular photoswitches
Cardiac cell modulation
Stretch-activated channels
title Role of stretch-activated channels in light-generated action potentials mediated by an intramembrane molecular photoswitch
title_full Role of stretch-activated channels in light-generated action potentials mediated by an intramembrane molecular photoswitch
title_fullStr Role of stretch-activated channels in light-generated action potentials mediated by an intramembrane molecular photoswitch
title_full_unstemmed Role of stretch-activated channels in light-generated action potentials mediated by an intramembrane molecular photoswitch
title_short Role of stretch-activated channels in light-generated action potentials mediated by an intramembrane molecular photoswitch
title_sort role of stretch activated channels in light generated action potentials mediated by an intramembrane molecular photoswitch
topic Light stimulation
Molecular photoswitches
Cardiac cell modulation
Stretch-activated channels
url https://doi.org/10.1186/s12967-024-05902-4
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