Department of Bioengineering, University of California San Diego La Jolla, CA, USA.
Department of Bioengineering, University of California San Diego La Jolla, CA, USA ; Department of Medicine, University of California San Diego La Jolla, CA, USA.
Front Pharmacol. 2014 May 16;5:110. doi: 10.3389/fphar.2014.00110. eCollection 2014.
Calcium/calmodulin-dependent protein kinase II (CaMKII) activity has been shown to contribute to arrhythmogenesis in a remarkably broad range of cardiac pathologies. Several of these involve significant structural and electrophysiologic remodeling, whereas others are due to specific channelopathies, and are not typically associated with arrhythmogenic changes to protein expression or cellular and tissue structure. The ability of CaMKII to contribute to arrhythmia across such a broad range of phenotypes suggests one of two interpretations regarding the role of CaMKII in cardiac arrhythmia: (1) some CaMKII-dependent mechanism is a common driver of arrhythmia irrespective of the specific etiology of the disease, or (2) these different etiologies expose different mechanisms by which CaMKII is capable of promoting arrhythmia. In this review, we dissect the available mechanistic evidence to explore these two possibilities and discuss how the various molecular actions of CaMKII promote arrhythmia in different pathophysiologic contexts.
钙/钙调蛋白依赖性蛋白激酶 II（CaMKII）的活性已被证明在多种心脏病理学中对心律失常的发生有显著作用。其中一些涉及到显著的结构和电生理重塑，而另一些则是由于特定的通道病变引起的，通常与心律失常时蛋白质表达或细胞和组织结构的变化无关。CaMKII 能够在如此广泛的表型中导致心律失常，这表明 CaMKII 在心脏心律失常中的作用有两种解释：（1）某种 CaMKII 依赖性机制是心律失常的共同驱动因素，而与疾病的具体病因无关，或者（2）这些不同的病因揭示了 CaMKII 能够促进心律失常的不同机制。在这篇综述中，我们剖析了现有的机制证据，以探讨这两种可能性，并讨论 CaMKII 的各种分子作用如何在不同的病理生理环境中促进心律失常。
