Fig. 2.

Model-simulated mdO₂^·− burst-induced early afterdepolarization (EAD) in a “beating” (0.5 Hz) cardiomyocyte. A: mitochondria-derived reactive oxygen species (mdROS) burst-elicited EAD (inset: EAD observed in a rabbit cardiomyocyte subjected to ROS perfusion; Ref. 59). B: comparison of APD₉₀ between model simulation (guinea pig) and experimental data (rabbit) under control and oxidative stress conditions {where APD₉₀ is the interval between the time of the maximum upstroke velocity of the action potential (AP), [dV/dt]_max, and 90% repolarization}. C– F: model simulated intracellular Ca²⁺ concentration ([Ca²⁺]_i) and SR Ca²⁺ concentration ([Ca²⁺]_SR) (C), RyR Ca²⁺ release (J_rel), and SERCA Ca²⁺ uptake (J_up) (D); Na⁺/Ca²⁺ exchanger current (I_NaCa) and Ca²⁺-sensitive nonspecific cationic current (I_nsCa) (E); and I_CaL (F) before and after a mdROS burst. The solid arrow in A represents the AP reversal; in C, D, and E, the [Ca²⁺]_i elevation, SR Ca²⁺ release, and activations of I_NaCa and I_nsCa caused by the mdO₂^·− burst, respectively; in F, the L-type Ca²⁺ current (I_CaL) reactivation. The dashed arrow in C, D, and E represents the second [Ca²⁺]_i elevation, SR Ca²⁺ release, and activations of I_NaCa and I_nsCa caused by I_CaL reactivation, respectively. The dashed lines represent ΔΨ_m and its depolarization represents the acute mdO₂^·− burst.