Figure 2.

Comparison of I_Ca- and caffeine-induced Ca²⁺ signals in hiPSC-CM from a healthy control subject and a CPVT1-afflicted patient with point mutation F2483I in RyR2. Currents were recorded with a 150ms or 250 ms step depolarizations from holding potential of −40 mV in 10 mV steps to +60 mV. (A) and (B) Left part of panels shows representative I_Ca and fluorescence traces where depolarization to 0mV rapidly activates Ca²⁺ release (black traces) while clamp pulses to +60 or +70 mV only activate rises in Ca²⁺ on repolarization (red traces). The right panel shows the I–V curves for I_Ca and the corresponding Ca²⁺ Fluo-4 signal from control and CPVT hiPSC-CM. (C) Representative caffeine-induced NCX currents and corresponding fluorescence Ca²⁺ signal from control and mutant hiPSC-CM. (D) Average values of caffeine-activated Ca²⁺ signals (top) and I_NCX currents (bottom) in each group. (E) Confocal image of immunofluorescence labeled RyR2 (green) in a small cluster of control hiPS-CM with DAPI-labeled nuclei (blue). Modified from [33]