Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 58, Issue -, Pages 172-181Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2012.11.011
Keywords
Stretch; Calcium sparks; EC coupling; Redox; NADPH oxidase; ROS
Categories
Funding
- National Institutes of Health (NIH) [T32 HL072751-07]
- NIH [R01 HL106059, R01 HL36974]
- Leducq North American-European Atrial Fibrillation Research Alliance
- European Union, Georg August University
- US patent for MyoTak
- [5K99HL114879-02]
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X-ROS signaling is a novel redox signaling pathway that links mechanical stress to changes in [Ca2+](i). This pathway is activated rapidly and locally within a muscle cell under physiological conditions, but can also contribute to Ca2+-dependent arrhythmia in the heart and to the dystrophic phenotype in the heart and skeletal muscle. Upon physiologic cellular stretch, microtubules serve as mechanotransducers to activate NADPH oxidase 2 in the transverse tubules and sarcolemmal membranes to produce reactive oxygen species (ROS). In the heart, the ROS acts locally to activate ryanodine receptor Ca2+ release channels in the junctional sarcoplasmic reticulum, increasing the Ca2+ spark rate and tuning excitation-contraction coupling. In the skeletal muscle, where Ca2+ sparks are not normally observed, the X-ROS signaling process is muted. However in muscular dystrophies, such as Duchenne Muscular Dystrophy and dysferlinopathy, X-ROS signaling operates at a high level and contributes to myopathy. Importantly, Ca2+ permeable stretch-activated channels are activated by X-ROS and contribute to skeletal muscle pathology. Here we review X-ROS signaling and mechanotransduction in striated muscle, and highlight important questions to drive future work on stretch-dependent signaling. We conclude that X-ROS provides an exciting mechanism for the mechanical control of redox and Ca2+ signaling, but much work is needed to establish its contribution to physiologic and pathophysiologic processes in diverse cell systems. This article is part of a Special Issue entitled Calcium Signaling in Heart. (C) 2012 Elsevier Ltd. All rights reserved.
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