X-ROS signaling in the heart and skeletal muscle: Stretch-dependent local ROS regulates [Ca 2 + ]i

• Published in: Journal of molecular and cellular cardiology Vol. 58; pp. 172 - 181
• Main Authors: Prosser, Benjamin L, Khairallah, Ramzi J, Ziman, Andrew P, Ward, Christopher W, Lederer, W.J
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-05-2013
• Subjects: Animals; Calcium - metabolism; Calcium Signaling; Calcium sparks; Cardiovascular; EC coupling; Humans; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Myocytes, Cardiac; NADPH oxidase; Oxidation-Reduction; Reactive Oxygen Species - metabolism; Redox; ROS; Ryanodine Receptor Calcium Release Channel - metabolism; Sarcolemma - metabolism; Sarcoplasmic Reticulum - metabolism; Signal Transduction; Stretch; Stretch; Redox; EC coupling; Calcium sparks; NADPH oxidase; ROS
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1016/j.yjmcc.2012.11.011

Abstract X-ROS signaling is a novel redox signaling pathway that links mechanical stress to changes in [Ca 2 + ]i . This pathway is activated rapidly and locally within a muscle cell under physiological conditions, but can also contribute to Ca 2 + -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 Ca 2 + release channels in the junctional sarcoplasmic reticulum, increasing the Ca 2 + spark rate and “tuning” excitation–contraction coupling. In the skeletal muscle, where Ca 2 + 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, Ca 2 + 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 Ca 2 + 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".