| First Author | Parks C | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 25372 | PubMed ID | 27150728 |
| Mgi Jnum | J:256719 | Mgi Id | MGI:6102067 |
| Doi | 10.1038/srep25372 | Citation | Parks C, et al. (2016) STIM1-dependent Ca(2+) microdomains are required for myofilament remodeling and signaling in the heart. Sci Rep 6:25372 |
| abstractText | In non-excitable cells stromal interaction molecule 1 (STIM1) is a key element in the generation of Ca(2+) 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 Ca(2+) signaling in the heart are not clearly established. Here, we have investigated the STIM1-associated Ca(2+) 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 Ca(2+) 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 Ca(2+) microdomains have a major impact on intracellular Ca(2+) homeostasis, cytoskeletal remodeling and cellular signaling, even when excitation-contraction coupling is present. |
