Fig. 2.

LCS can trigger EADs. (A) EADs evoked by pacing-pause protocol. During repolarization, an initial V_m inflection at ∼ −20 mV generates EADs (Top), and numerous LCS create oscillatory Ca²⁺ release (Bottom). (B) Calculation of I_net for a typical HF AP. The filled region indicates where the greatest number of LCS occur (A and Fig. 4E) and corresponds to an I_net of ∼0.18 pA/pF. Any balancing current that counteracts I_net (i.e., −I_net, Bottom) will stop repolarization (SI Appendix, Fig. S5). (C) Failing AP with voltage-clamp steps used to probe Ca²⁺ and currents underlying EADs. (D) During the AP steps, LCS-triggered Ca²⁺ waves (Top) and inward currents (black trace) appear. Dashed line shows the inward current that balances I_net in B and could therefore stop repolarization. This current occurs when LCS are about to initiate Ca²⁺ waves. (E) Example of apparently chaotic Ca²⁺ during EADs in an HF cell (Top). Image processing reveals many LCS and Ca²⁺ ripples during V_m oscillations (red trace). The filled regions show where the depolarizing current (I_net) is increasing, and this corresponds to increasing Ca²⁺ (blue) and LCS activity (orange bars).