Calmodulinopathy: Functional Effects of CALM Mutations and Their Relationship With Clinical Phenotypes

Frontiers in Cardiovascular Medicine

Beatrice Badone¹ 

关键词: calmodulin mutations;    ion channels;    repolarization;    Ca2+ handling;    arrhythmia mechanisms;   

DOI  :  10.3389/fcvm.2018.00176

学科分类：心脏病和心血管学

来源: Frontiers

【 摘 要 】

In spite of the widespread role of calmodulin (CaM) in cellular signaling, CaM mutations lead specifically to cardiac manifestations, characterized by remarkable electrical instability and a high incidence of sudden death at young age. Penetrance of the mutations is surprisingly high, thus postulating a high degree of functional dominance. According to the clinical patterns, arrhythmogenesis in CaM mutations can be attributed, in the majority of cases, to either prolonged repolarization (as in long-QT syndrome, LQTS phenotype), or to instability of the intracellular Ca2+ store (as in catecholamine-induced tachycardias, CPVT phenotype). This review discusses how mutations affect CaM signaling function and how this may relate to the distinct arrhythmia phenotypes/mechanisms observed in patients; this involves mechanistic interpretation of negative dominance and mutation-specific CaM-target interactions. Knowledge of the mechanisms involved may allow critical approach to clinical manifestations and aid in the development of therapeutic strategies for “calmodulinopathies,” a recently identified nosological entity.

【 授权许可】

CC BY