Why the study?
Although calmodulin mutation was assumed to be lethal, mutations discovered in infants with recurrent cardiac arrest linked CaM defects to cardiac arrhythmias.
Provides a comprehensive status report on the biochemical and structural mechanisms by which Calmodulin mutations contribute to cardiac arrhythmias.
Calmodulin (CaM) is a ubiquitous intracellular Ca2+ 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 CALM 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.
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Chazin et al. (2020) studied this question.
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