Optical control of cardiac electrophysiology by the photochromic ligand azobupivacaine 2.

Autor: Fehrentz T; Institute of Neural and Sensory Physiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.; Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany., Amin E; Institute of Neural and Sensory Physiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Görldt N; Institute of Neural and Sensory Physiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Strasdeit T; Institute of Neural and Sensory Physiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Moussavi-Torshizi SE; Institute of Neural and Sensory Physiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Leippe P; Department of Chemical Biology, Max Planck Institute for Medical Research, Heidelberg, Germany., Trauner D; Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Meyer C; Institute of Neural and Sensory Physiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.; Division of Cardiology, Angiology and Intensive Care, EVK Düsseldorf, Cardiac Neuro- and Electrophysiology Research Consortium (cNEP), Düsseldorf, Germany., Frey N; Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany., Sasse P; Institute of Physiology I, Medical Faculty, University of Bonn, Bonn, Germany., Klöcker N; Institute of Neural and Sensory Physiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2024 Nov 14. Date of Electronic Publication: 2024 Nov 14.
DOI: 10.1111/bph.17394
Abstrakt: Background and Purpose: Patients suffering from ischaemic heart disease and heart failure are at high risk of recurrent ventricular arrhythmias (VAs), eventually leading to sudden cardiac death. While high-voltage shocks delivered by an implantable defibrillator may prevent sudden cardiac death, these interventions themselves impair quality of life and raise both morbidity and mortality, which accentuates the need for developing novel defibrillation techniques.
Experimental Approach: Photopharmacology allows for reversible control of biological processes by light. When relying on synthetic and externally applied chromophores, it renders genetic modification of target cells dispensable and may hence be advantageous over optogenetic approaches. Here, the photochromic ligand azobupivacaine 2 (AB2) was probed as a modulator of cardiac electrophysiology in an ex vivo intact mouse heart model.
Key Results: By reversibly blocking voltage-gated Na + and K + channels, photoswitching of AB2 modulated both the ventricular effective refractory period and the conduction velocity in native heart tissue. Moreover, photoswitching of AB2 was able to convert VA into sinus rhythm.
Conclusion and Implications: The present study provides the first proof of concept that AB2 enables gradual control of cardiac electrophysiology by light. AB2 may hence open the door to the development of an optical defibrillator based on photopharmacology.
(© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
Databáze: MEDLINE
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