Figure 5. Optogenetic protocols to suppress cardiomyocyte excitability.

(A and B) Whole-cell patch-clamp recordings from ChR2-expressing (A) or ACR2-expressing (B) hiPSC-CMs. Notice how continuous prolonged 1.3 mW/mm² blue light illumination clamps membrane potential to either a depolarized (in the case of ChR2; A) or hyperpolarized (ACR2; B) potential and suppresses spontaneous AP generation. Scale bar: 40 mV. (C) Representative optical AP recording (using voltage-dye imaging), acquired during continuous electrical field stimulation (1 Hz) of hiPSC-CMs expressing either ChR2 (representing 7 experiments, top panel), ACR2 (representing 19 experiments, middle panel), or eGFP (representing 17 experiments, bottom panel). Note that prolonged illumination with 1.3 mW/mm² blue light completely suppressed AP development in ChR2-expressing (top panel) and ACR2-expressing (middle panel) hiPSC-CMs. The same illumination protocol, however, did not affect control eGFP-expressing hiPSC-CMs (bottom panel). Illumination timing is represented in all tracings by the blue background.