Abstract 026: Optical Recording of Cardiac Action Potentials from Human Induced Pluripotent Stem Cell Derived Cardiomyocytes

The electrically excitable properties of cardiomyocytes stem from the activity of ion channels that allow the coordinated entry of ions to generate cardiac action potentials. Disruptions in ion channel function either by drugs or gene mutations can lead to cardiac arrhythmias. The ability to screen drugs or gene mutations rapidly for effects on the cardiac action potential would be of interest for both drug discovery as well as for studies of ion channel function; however, the time-consuming and technically challenging nature of conventional patch clamping can limit the ability to perform high throughput screens. Archaerhodopsin3, or Arch, is an Archaebacterial variant of the membrane protein bacteriorhodopsin that binds a retinal fluorophore whose signal is rapidly responsive to changes in membrane potential. Here, we report the use of Arch to optically record action potentials from human induced pluripotent stem cell-derived cardiomyocytes. Human induced pluripotent stem cells that stably express Arch were generated and then differentiated into cardiomyocytes. As compared to patch clamping, Arch faithfully reproduces many of the key features of cardiac action potentials and may be a tool to be used for high throughput electrophysiological screens of cardiomyocytes.