Departments of Biochemistry, Chemistry, and Center for Structural Biology, Vanderbilt University, Nashville, TN 37240, USA.
Dorothy M. Davis Heart and Lung Research Institute, The Ohio State Wexner Medical Center, Columbus, OH 43210, USA.
Int J Mol Sci. 2020 Feb 19;21(4):1418. doi: 10.3390/ijms21041418.
Calmodulin (CaM) is a ubiquitous intracellular Ca sensing protein that modifies gating of numerous ion channels. CaM has an extraordinarily high level of evolutionary conservation, which led to the fundamental assumption that mutation would be lethal. However, in 2012, complete exome sequencing of infants suffering from recurrent cardiac arrest revealed de novo mutations in the three human genes. The correlation between mutations and pathophysiology suggests defects in CaM-dependent ion channel functions. Here, we review the current state of the field for all reported CaM mutations associated with cardiac arrhythmias, including knowledge of their biochemical and structural characteristics, and progress towards understanding how these mutations affect cardiac ion channel function.
钙调蛋白（CaM）是一种普遍存在的细胞内 Ca 感应蛋白，可调节众多离子通道的门控。CaM 的进化保守性极高，这导致了一个基本假设，即突变将是致命的。然而，在 2012 年，对反复发生心脏骤停的婴儿进行的完整外显子组测序揭示了三种人类基因中的新生突变。突变与病理生理学之间的相关性表明，CaM 依赖性离子通道功能存在缺陷。在这里，我们综述了与心律失常相关的所有报道的 CaM 突变的研究现状，包括对其生化和结构特征的了解，以及在理解这些突变如何影响心脏离子通道功能方面的进展。
