long-term-blood-pressure-measurement-freely-moving-mice-using

Long-term Blood Pressure Measurement in Freely Moving Mice Using Telemetry

During the development of new vasoactive agents, arterial blood pressure monitoring is crucial for evaluating the efficacy of the new proposed drugs. ...

University of Tennessee Health Sciences Center

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.

Cory Parks

Biography

JoVE Journal Publications

Other Publications