Cardiac calsequestrin: quest inside the SR.

摘要

Although calsequestrin (CASQ), a major sarcoplasmic reticulum (SR) Ca~2+ binding protein, was discovered more than 30 years ago, its precise roles and modes of operation in both skeletal and cardiac muscle remain to be elucidated (Rios, 2009, this issue; Knollmann, 2009, this issue). Recent years witnessed a significant surge of interest in this Ca~2+ binding protein after mutations in the gene encoding the cardiac isoform of calsequestrin (CASQ2) were linked to exercise-induced cardiac death due to catecholaminergic polymorphic ventricular tachycardia (CPVT) (Postma et al. 2002; Eldar et al 2003). Surprisingly, humans and genetically altered mice devoid of CASQ2 preserve nearly normal cardiac structure and function but develop lethal arrhythmias under conditions of adrenergic stimulation (Postma et al. 2002; Knollmann et al. 2006; Song etal. 2007). Here we provide a brief overview of our current understanding of the functional role and mode of operation of CASQ2 in the heart, of how hearts missing CASQ2 cope in the absence of this protein and of the mechanisms of CPVT.