In heart muscle, the physiological function of IP₃-induced Ca²⁺ release (IP₃ICR) from the sarcoplasmic reticulum (SR) is still the subject of intense study. A role of IP₃ICR may reside in modulating Ca²⁺-dependent cardiac arrhythmogenicity. Here we observe the propensity of spontaneous intracellular Ca²⁺ waves (SCaW) driven by Ca²⁺-induced Ca²⁺ release (CICR) in ventricular myocytes as a correlate of arrhythmogenicity on the organ level. We observe a dual mode of action of IP₃ICR on SCaW generation in an IP₃R overexpression model. This model shows a mild cardiac phenotype and mimics pathophysiological conditions of increased IP₃R activity. In this model, IP₃ICR was able to increase or decrease the occurrence of SCaW depending on global Ca²⁺ activity. This IP₃ICR-based regulatory mechanism can operate in two “modes” depending on the intracellular CICR activity and efficiency (e.g. SCaW and/or local Ryanodine Receptor (RyR) Ca²⁺ release events, respectively): a) in a mode that augments the CICR mechanism at the cellular level, resulting in improved excitation-contraction coupling (ECC) and ultimately better contraction of the myocardium, and b) in a protective mode in which the CICR activity is curtailed to prevent the occurrence of Ca²⁺ waves at the cellular level and thus reduce the probability of arrhythmogenicity at the organ level.

在心肌中，IP ₃诱导的肌浆网(SR) 释放Ca ²⁺ (IP ₃ ICR) 的生理功能仍然是深入研究的主题。_{IP 3} ICR的作用可能在于调节 Ca ²⁺依赖性心律失常。在这里，我们观察心室肌细胞中由 Ca 2+ 诱导的 Ca 2+ 释放 (CICR) 驱动的自发细胞内 Ca 2+ 波^{( SCaW} )^的倾向，作为器官水平上致心律失常的相关性。_{我们在 IP 3 R 过表达模型中观察到 IP 3} ICR 对 SCaW 生成的双重作用模式。该模型显示出轻微的心脏表型，并模拟 IP ₃ R 活性增加的病理生理条件。在此模型中，IP ₃ ICR 能够根据整体 Ca ²⁺活性增加或减少 SCaW 的发生。这种基于 IP ₃ ICR 的调节机制可以在两种“模式”下运行，具体取决于细胞内 CICR 活性和效率（例如，分别为 SCaW 和/或局部 Ryanodine 受体 (RyR) Ca ²⁺释放事件）：在细胞水平上增强 CICR 机制，从而改善兴奋-收缩耦合 (ECC) 并最终更好地收缩心肌，以及 b) 处于保护模式，其中 CICR 活性被削弱以防止 Ca 2+ 波^的发生在细胞水平上，从而降低在器官水平上致心律失常的可能性。