Figure 20.

Energetic dysfunction and arrhythmic phenotype. Possible simplified relationships between (A) energetic dysfunction associated with ischemic conditions, cardiac failure, ageing and diabetes, (B) mitochondrial dysfunction associated with ROS production, altered NAD⁺/NADH, and ATP/ADP and their possible consequences for (C) RyR2-mediated release of SR Ca²⁺ leading to increased [Ca²⁺]_i, and NCX and DAD triggering activity, and (D) Na⁺ and K⁺ channel activity affecting AP excitation, propagation, and recovery potentially resulting in (E) substrate that can be potentially triggered to give arrhythmic phenotypes.