Approaching the mechanistic insights towards the genesis of intracellular calcium transient alternans - a simulation study

Mechanical contraction alternans of the heart is associated with fatal cardiac death. It is manifested by T-wave alternans in the ECG, and is thought to be possibly related to intracellular Ca²⁺ transient alternans released from the sarcoplasmic reticulum (SR). However, it is unclear yet how beat-to-beat alternans of intracellular Ca²⁺ transient is produced. In this study investigated the mechanism(s) underlying the genesis of intracellular Ca²⁺ alternans produced at slow pacing rates by using a mathematical model of a spatially extended cardiac cell with a cluster of coupled ryanodine receptor (RyR) elements. It was shown that the intracellular Ca²⁺ alternans was generated by propagating waves of Ca²⁺ release and sustained through alternation of SR Ca²⁺ content that has a stiff relationship with the Ca²⁺ transient. This study provides novel and fundamental insights to understand mechanisms that may underlie intracellular Ca²⁺ alternans without the need for refractoriness of L-type Ca or RyR channels under rapid pacing.