Figure. 1. Ca²⁺ induced Ca²⁺ release (CICR), store-overload-induced Ca²⁺ release (SOICR) and triggered arrhythmia.

The left part of the diagram (in blue) depicts the mechanism of CICR, in which an action potential activates the voltage-dependent L-type Ca²⁺ channel, leading to a small Ca²⁺ influx. This Ca²⁺ entry opens the RyR2 channel in the sarcoplasmic reticulum (SR), resulting in SR Ca²⁺ release and muscle contraction. The right part of the diagram (in red) denotes the mechanism of SOICR, in which spontaneous SR Ca²⁺ release or Ca²⁺ spillover occurs under conditions of SR Ca²⁺ overload caused, for example, by stress via the beta-adrenergic receptor (b-AR)/protein kinase A (PKA)/phospholamban (PLB) signaling pathway. SOICR can activate the Na+/Ca²⁺ exchanger (Na/CaX), which, in turn, can lead to delayed afterdepolarizations (DADs) and triggered activities. (Illustration Credit: Cosmocyte/Ben Smith).