Voltage Imaging of Cardiac Cells and Tissue Using the Genetically Encoded Voltage Sensor Archon1

Sanaya N Shroff; Shoshana L Das; Hua-An Tseng; Jad Noueihed; Fernando Fernandez; John A White; Christopher S Chen; Xue Han

doi:10.1016/j.isci.2020.100974

Voltage Imaging of Cardiac Cells and Tissue Using the Genetically Encoded Voltage Sensor Archon1

iScience. 2020 Apr 24;23(4):100974. doi: 10.1016/j.isci.2020.100974. Epub 2020 Mar 11.

Authors

Sanaya N Shroff¹, Shoshana L Das², Hua-An Tseng¹, Jad Noueihed¹, Fernando Fernandez¹, John A White¹, Christopher S Chen³, Xue Han⁴

Affiliations

¹ Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
² Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA; Harvard-MIT Program in Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
³ Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. Electronic address: chencs@bu.edu.
⁴ Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA. Electronic address: xuehan@bu.edu.

Abstract

Precise measurement of action potentials (APs) is needed to observe electrical activity and cellular communication within cardiac tissue. Voltage-sensitive dyes (VSDs) are traditionally used to measure cardiac APs; however, they require acute chemical addition that prevents chronic imaging. Genetically encoded voltage indicators (GEVIs) enable long-term studies of APs without the need of chemical additions, but current GEVIs used in cardiac tissue exhibit poor kinetics and/or low signal to noise (SNR). Here, we demonstrate the use of Archon1, a recently developed GEVI, in hiPSC-derived cardiomyocytes (CMs). When expressed in CMs, Archon1 demonstrated fast kinetics comparable with patch-clamp electrophysiology and high SNR significantly greater than the VSD Di-8-ANEPPS. Additionally, Archon1 enabled monitoring of APs across multiple cells simultaneously in 3D cardiac tissues. These results highlight Archon1's capability to investigate the electrical activity of CMs in a variety of applications and its potential to probe functionally complex in vitro models, as well as in vivo systems.

Keywords: Bioelectronics; Biotechnology; Electronic Materials; Technical Aspects of Cell Biology.

Abstract

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