STIM1-dependent Ca2+ microdomains are required for myofilament remodeling and signaling in the heart

Cory Parks, Mohammad Afaque Alam, Ryan Sullivan, Salvatore Mancarella

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

In non-excitable cells stromal interaction molecule 1 (STIM1) is a key element in the generation of Ca2+ signals that lead to gene expression, migration and cell proliferation. A growing body of literature suggests that STIM1 plays a key role in the development of pathological cardiac hypertrophy. However, the precise mechanisms involving STIM-dependent Ca2+ signaling in the heart are not clearly established. Here, we have investigated the STIM1-associated Ca2+ signals in cardiomyocytes and their relevance to pathological cardiac remodeling. We show that mice with inducible, cardiac-restricted, ablation of STIM1 exhibited left ventricular reduced contractility, which was corroborated by impaired single cell contractility. The spatial properties of STIM1-dependent Ca 2+ signals determine restricted Ca2+ microdomains that regulate myofilament remodeling and activate spatially segregated pro-hypertrophic factors. Indeed, mice lacking STIM1 showed less adverse structural remodeling in response to pressure overload-induced cardiac hypertrophy. These results highlight how STIM1-dependent Ca2+ microdomains have a major impact on intracellular Ca2+ homeostasis, cytoskeletal remodeling and cellular signaling, even when excitation-contraction coupling is present.

Original languageEnglish (US)
Article number25372
JournalScientific Reports
Volume6
DOIs
StatePublished - May 6 2016

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Myofibrils
Cardiomegaly
Excitation Contraction Coupling
Stromal Interaction Molecule 1
Cardiac Myocytes
Cell Communication
Homeostasis
Cell Proliferation
Gene Expression
Pressure

All Science Journal Classification (ASJC) codes

  • General

Cite this

STIM1-dependent Ca2+ microdomains are required for myofilament remodeling and signaling in the heart. / Parks, Cory; Alam, Mohammad Afaque; Sullivan, Ryan; Mancarella, Salvatore.

In: Scientific Reports, Vol. 6, 25372, 06.05.2016.

Research output: Contribution to journalArticle

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