Hypertrophic cardiomyopathy mutations increase myofilament Ca²⁺ buffering, alter intracellular Ca²⁺ handling, and stimulate Ca²⁺-dependent signaling.

ABSTRACT: Mutations in thin filament regulatory proteins that cause hypertrophic cardiomyopathy (HCM) increase myofilament Ca²⁺ sensitivity. Mouse models exhibit increased Ca²⁺ buffering and arrhythmias, and we hypothesized that these changes are primary effects of the mutations (independent of compensatory changes) and that increased Ca²⁺ buffering and altered Ca²⁺ handling contribute to HCM pathogenesis via activation of Ca²⁺-dependent signaling. Here, we determined the primary effects of HCM mutations on intracellular Ca²⁺ handling and Ca²⁺-dependent signaling in a model system possessing Ca²⁺-handling mechanisms and contractile protein isoforms closely mirroring the human environment in the absence of potenti

SUBMITTER: Robinson P 

PROVIDER: S-EPMC6036197 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature