Optical Interrogation of Sympathetic Neuronal Effects on Macroscopic Cardiomyocyte Network Dynamics
Rebecca-Ann B. Burton,
Jakub Tomek,
Christina M. Ambrosi,
Hege E. Larsen,
Amy R. Sharkey,
Rebecca A. Capel,
Alexander D. Corbett,
Samuel Bilton,
Aleksandra Klimas,
Guy Stephens,
Maegan Cremer,
Samuel J. Bose,
Dan Li,
Giuseppe Gallone,
Neil Herring,
Edward O. Mann,
Abhinav Kumar,
Holger Kramer,
Emilia Entcheva,
David J. Paterson,
Gil Bub
Affiliations
Rebecca-Ann B. Burton
University of Oxford, Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK; University of Oxford, Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, Parks Road, Oxford OX1 3PT, UK; Corresponding author
Jakub Tomek
University of Oxford, Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, Parks Road, Oxford OX1 3PT, UK
Christina M. Ambrosi
The George Washington University, Department of Biomedical Engineering, Washington, DC 20052, USA
Hege E. Larsen
University of Oxford, Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, Parks Road, Oxford OX1 3PT, UK
Amy R. Sharkey
University of Oxford, Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, Parks Road, Oxford OX1 3PT, UK
Rebecca A. Capel
University of Oxford, Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK
Alexander D. Corbett
University of Exeter, Physics and Astronomy, Exeter EX4 4QL, UK
Samuel Bilton
University of Oxford, Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, Parks Road, Oxford OX1 3PT, UK
Aleksandra Klimas
The George Washington University, Department of Biomedical Engineering, Washington, DC 20052, USA
Guy Stephens
University of Oxford, Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, Parks Road, Oxford OX1 3PT, UK
Maegan Cremer
University of Oxford, Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK
Samuel J. Bose
University of Oxford, Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK
Dan Li
University of Oxford, Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, Parks Road, Oxford OX1 3PT, UK
Giuseppe Gallone
University of Oxford, Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, Parks Road, Oxford OX1 3PT, UK; Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany
Neil Herring
University of Oxford, Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, Parks Road, Oxford OX1 3PT, UK
Edward O. Mann
University of Oxford, Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, Parks Road, Oxford OX1 3PT, UK
Abhinav Kumar
University of Oxford, Department of Biochemistry, Glycobiology Institute, Oxford, UK
Holger Kramer
University of Oxford, Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, Parks Road, Oxford OX1 3PT, UK
Emilia Entcheva
The George Washington University, Department of Biomedical Engineering, Washington, DC 20052, USA
David J. Paterson
University of Oxford, Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, Parks Road, Oxford OX1 3PT, UK
Gil Bub
University of Oxford, Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, Parks Road, Oxford OX1 3PT, UK; McGill University, Department of Physiology, McIntyre Medical Sciences Building, Room 1128, 3655 Promenade Sir William Osler, Montréal, QC H3G 1Y6, Canada; Corresponding author
Summary: Cardiac stimulation via sympathetic neurons can potentially trigger arrhythmias. We present approaches to study neuron-cardiomyocyte interactions involving optogenetic selective probing and all-optical electrophysiology to measure activity in an automated fashion. Here we demonstrate the utility of optical interrogation of sympathetic neurons and their effects on macroscopic cardiomyocyte network dynamics to address research targets such as the effects of adrenergic stimulation via the release of neurotransmitters, the effect of neuronal numbers on cardiac behavior, and the applicability of optogenetics in mechanistic in vitro studies. As arrhythmias are emergent behaviors that involve the coordinated activity of millions of cells, we image at macroscopic scales to capture complex dynamics. We show that neurons can both decrease and increase wave stability and re-entrant activity in culture depending on their induced activity—a finding that may help us understand the often conflicting results seen in experimental and clinical studies.
