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Front. Physiol. | doi: 10.3389/fphys.2018.01806

Cardiac Electrophysiological Effects of Light-Activated Chloride Channels

 Ramona A. Kopton1, 2, 3, Jonathan S. Baillie4, Sara A. Rafferty4, Robin Moss1, 2, Callum M. Zgierski-Johnston1, 2,  Sergey V. Prykhozhij4, Matthew R. Stoyek4, Frank Smith4,  Peter Kohl1, 2,  T A. Quinn4 and  Franziska Schneider-Warme1, 2*
  • 1Universitäts-Herzzentrum Freiburg, Germany
  • 2Medizinische Fakultät, Albert Ludwigs University of Freiburg, Germany
  • 3Faculty of Biology, University of Freiburg, Germany
  • 4Department of Physiology and Biophysics, Dalhousie University, Canada

During the last decade, optogenetics has emerged as a paradigm-shifting technique to monitor and 18 steer the behavior of specific cell types in excitable tissues, including the heart. Activation of cation-19 conducting channelrhodopsins (ChR) leads to membrane depolarization, allowing one to effectively 20 trigger action potentials (AP) in cardiomyocytes. In contrast, the quest for optogenetic tools for 21 hyperpolarization-induced inhibition of AP generation has remained challenging. The green-light 22 activated ChR from Guillardia theta (GtACR1) mediates Cl--driven photocurrents that have been 23 shown to silence AP generation in different types of neurons. It has been suggested, therefore, to be a 24 suitable tool for inhibition of cardiomyocyte activity. Using single-cell electrophysiological 25 recordings and contraction tracking, as well as intracellular microelectrode recordings and in vivo 26 optical recordings of whole hearts, we find that GtACR1 activation by prolonged illumination arrests 27 cardiac cells in a depolarized state, thus inhibiting re-excitation. In line with this, GtACR1 activation 28 by transient light pulses elicits AP in isolated rabbit cardiomyocytes and in spontaneously beating 29 intact hearts of zebrafish. Our results show that GtACR1 inhibition of AP generation is caused by cell 30 depolarization. While this does not address the need for optogenetic silencing through physiological 31 means (i.e. hyperpolarization), GtACR1 is a potentially attractive tool for activating cardiomyocytes 32 by transient light-induced depolarization.

Keywords: Heart, optogenetics, action potential, GtACR1, natural anion channelrhodopsin, Zebrafish

Received: 30 Sep 2018; Accepted: 30 Nov 2018.

Edited by:

Ming Lei, University of Oxford, United Kingdom

Reviewed by:

Christopher Huang, University of Cambridge, United Kingdom
Claudia Richter, Max-Planck-Institut für Dynamik und Selbstorganisation, Germany  

Copyright: © 2018 Kopton, Baillie, Rafferty, Moss, Zgierski-Johnston, Prykhozhij, Stoyek, Smith, Kohl, Quinn and Schneider-Warme. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Franziska Schneider-Warme, Universitäts-Herzzentrum Freiburg, Bad Krozingen, Germany, franziska.schneider@universitaets-herzzentrum.de