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.

Badone, B., Ronchi, C., Kotta, M., Sala, L., Ghidoni, A., Crotti, L., et al. (2018). Calmodulinopathy: Functional Effects of CALM Mutations and Their Relationship With Clinical Phenotypes. FRONTIERS IN CARDIOVASCULAR MEDICINE, 5 [10.3389/fcvm.2018.00176].

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

Badone, Beatrice
Primo
;
Ronchi, Carlotta;Sala, Luca;Crotti, Lia;Zaza, Antonio
2018

Abstract

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.
Articolo in rivista - Review Essay
arrhythmia mechanisms; Ca; 2+; handling; calmodulin mutations; ion channels; repolarization;
Ca2+ handling; arrhythmia mechanisms; calmodulin mutations; ion channels; repolarization
English
2018
5
176
open
Badone, B., Ronchi, C., Kotta, M., Sala, L., Ghidoni, A., Crotti, L., et al. (2018). Calmodulinopathy: Functional Effects of CALM Mutations and Their Relationship With Clinical Phenotypes. FRONTIERS IN CARDIOVASCULAR MEDICINE, 5 [10.3389/fcvm.2018.00176].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/218258
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