Figure 8.

Schematic presentation of proposed cellular mechanisms of SK-mediated protection from Ca²⁺-dependent ventricular arrhythmia. (i) Functional upregulation of SK2 and 3 in the plasma membrane limits disease-related prolongation of APD and reduces Ca²⁺-dependent EADs and DADs countering I_NCX; (ii) Functional upregulation of mitochondria-targeted SK2 attenuates disease-related increase in mito-ROS. Pharmacological enhancement of SK2 reduces mito-ROS resulting in normalization of the oxidative state of RyR, stabilization of RyR-mediated Ca²⁺release and abolishment of DAD-driving SCWs.