Figure 5
Generalizing OptoGap for different relative excitability between donor (D) and host (H) cells. (a) OptoGap assay sensitivity (σ) vs. inter-cellular gap junction conductance for tandem cell unit simulations in which the donor cell has relatively weak electrophysiological excitability (i.e., ChR2-cFB). See text for explanation of σ metric. Different-coloured lines show the same relationship but with gradually reduced host cell excitability (via INa blockade). (b) Same as (a) but for donor cells with a higher baseline level of excitability (ChR2-hiPSC-CM); minor variation between curves. (c) Same as (b) but with gradually reduced donor cell excitability instead of host excitability. (d) Same as (b) but with both donor and host cell excitability reduced by the same amount for each line. (e) Conceptual schematics for different D/H configurations. I: When light-sensitive D-cells have lower excitability than the H-tissue (similar to the case of ChR2-cFB among non-transduced cardiomyocytes), the OptoGap test follows an exponentially decreasing curve of energy as function of cell–cell-coupling. Corresponds most closely to the orange line (100% INa) in panel (a). II: When light-sensitive D-cells have higher excitability than the H-tissue (similar to the case of cell delivery of ChR2-iPSC-cardiomyocytes into the adult myocardium), the OptoGap test follows an exponentially increasing curve of energy as function of cell–cell-coupling. Corresponds most closely to the orange line (100% INa) in panel (b).
