Figure 2: Drug testing considerations and computational analysis of the use of optogenetic tools.
From: OptoDyCE as an automated system for high-throughput all-optical dynamic cardiac electrophysiology
A comparison of actuators (for example, ChR2) versus optogenetic sensors (for example, VSFP2.3) in human ventricular myocytes. A fast optogenetic actuator acts as a stimulation impulse and is ‘time-detached’ from the electrophysiological response (a), and therefore a hypothetical drug action that affects ChR2 current amplitude and/or kinetics (b) has minimal effect on the optically triggered APs (c) and CTs (d), if light irradiances are adjusted to provide supra-threshold currents (e). Even extreme drug interference with ChR2 off-kinetics results in minor (5%) APD prolongation (c) due to re-activation of inward ChR2 current during repolarization (f). In contrast, an optogenetic sensor, for example, VSFP2.3, is fully ‘temporally convolved’ with the electrophysiological response (a), and even a mild drug action on the sensor can profoundly influence the electrophysiological readout (g).
