Stressed out: the skeletal muscle ryanodine receptor as a target of stress
Andrew M. Bellinger, … , Marco Mongillo, Andrew R. Marks
Andrew M. Bellinger, … , Marco Mongillo, Andrew R. Marks
Published February 1, 2008
Citation Information: J Clin Invest. 2008;118(2):445-453. https://doi.org/10.1172/JCI34006.
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Stressed out: the skeletal muscle ryanodine receptor as a target of stress

Abstract

Over the past century, understanding the mechanisms underlying muscle fatigue and weakness has been the focus of much investigation. However, the dominant theory in the field, that lactic acidosis causes muscle fatigue, is unlikely to tell the whole story. Recently, dysregulation of sarcoplasmic reticulum (SR) Ca2+ release has been associated with impaired muscle function induced by a wide range of stressors, from dystrophy to heart failure to muscle fatigue. Here, we address current understandings of the altered regulation of SR Ca2+ release during chronic stress, focusing on the role of the SR Ca2+ release channel known as the type 1 ryanodine receptor.

Authors

Andrew M. Bellinger, Marco Mongillo, Andrew R. Marks

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Figure 2

Stress responses in skeletal muscle during E-C coupling.

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Stress responses in skeletal muscle during E-C coupling. Depolarization ...
Depolarization of the T-tubule membrane activates Cav1.1, triggering SR Ca2+ release through RyR1 and leading to sarcomere contraction, a process known as E-C coupling. Intracellular signaling pathways activated in skeletal muscle by pathological stress affect RyR1 function and alter E-C coupling. Stress-induced RyR1 dysfunction can result in SR Ca2+ leak, which potentially activates numerous Ca2+-dependent cellular damage mechanisms. AC, adenylate cyclase.