Department of Physiology, University of Bern, Buehlplatz 5, CH 3012 Bern, Switzerland; Department of Emergency Medicine (Notfallzentrum) Inselspital - University of Bern, Freiburgstrasse 10, CH 3010 Bern, Switzerland.
Department of Physiology, University of Bern, Buehlplatz 5, CH 3012 Bern, Switzerland.
J Mol Cell Cardiol. 2024 Jan;186:107-110. doi: 10.1016/j.yjmcc.2023.11.009. Epub 2023 Nov 20.
In heart muscle, the physiological function of IP-induced Ca release (IPICR) from the sarcoplasmic reticulum (SR) is still the subject of intense study. A role of IPICR may reside in modulating Ca-dependent cardiac arrhythmogenicity. Here we observe the propensity of spontaneous intracellular Ca waves (SCaW) driven by Ca-induced Ca release (CICR) in ventricular myocytes as a correlate of arrhythmogenicity on the organ level. We observe a dual mode of action of IPICR on SCaW generation in an IPR overexpression model. This model shows a mild cardiac phenotype and mimics pathophysiological conditions of increased IPR activity. In this model, IPICR was able to increase or decrease the occurrence of SCaW depending on global Ca activity. This IPICR-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) Ca 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 Ca waves at the cellular level and thus reduce the probability of arrhythmogenicity at the organ level.
在心肌中，肌质网（SR）中 IP 诱导的 Ca 释放（IPICR）的生理功能仍然是激烈研究的主题。IPICR 的作用可能在于调节 Ca 依赖性心律失常性。在这里，我们观察了心室肌细胞中由 Ca 诱导的 Ca 释放（CICR）驱动的自发性细胞内 Ca 波（SCaW）的倾向，作为器官水平心律失常性的相关指标。我们观察到在 IPR 过表达模型中，IPICR 对 SCaW 产生的双重作用模式。该模型表现出轻度的心脏表型，并模拟了 IPR 活性增加的病理生理条件。在该模型中，IPICR 能够根据整体 Ca 活性增加或减少 SCaW 的发生。这种基于 IPR 的调节机制可以根据细胞内 CICR 活性和效率在两种“模式”下运行（例如，分别为 SCaW 和/或局部 Ryanodine Receptor（RyR）Ca 释放事件）：a）在增强细胞水平上的 CICR 机制的模式下，导致更好的兴奋-收缩偶联（ECC），最终使心肌收缩更好，b）在保护性模式下，CICR 活性被削弱，以防止细胞水平发生 Ca 波，从而降低器官水平心律失常的可能性。
