Nov. 22, 2010 The heart beats stronger and faster in situations of stress. If the stress is experienced for only a short time it promotes the fight-or-flight response that enables us to endure physical and emotional exercise, but if it is prolonged it leads to heart failure. Two reports from the laboratory of Andrew Marks, at Columbia University, New York, provide new insight into the mechanisms underlying the response of the mouse heart to the stress.
Previous data from Marks' laboratory has indicated that a key part of the response of the heart to prolonged stress is the modification (by phosphorylation on building block serine 2808) of the protein RyR2. In the first of the new reports, Marks and colleagues generated mice in which serine 2808 was replaced with a building block that cannot be phosphorylated and found that their hearts did not beat stronger and faster in response to a chemical substitute for short term stress.
Thus, they conclude that phosphorylation of RyR2 at serine 2808 is important for the short-term response to stress, the fight-or-flight response. In the second paper, they generated mice in which serine 2808 was replaced with a building block that mimics phosphorylated serine. These mice developed heart problems as they aged that could be mitigated with a beta-blocker (the main drugs used to treat heart failure). Thus, Marks and colleagues conclude that one of the mechanisms by which beta-blockers benefit patients with heart failure is by targeting phosphorylated RyR2.
In an accompanying commentary, Thomas Eschenhagen, at the University Medical Center Hamburg Eppendorf, Germany, discusses how the new data generated by Marks and colleagues might help resolve controversies in the field.
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- Jian Shan, Alexander Kushnir, Matthew J. Betzenhauser, Steven Reiken, Jingdong Li, Stephan E. Lehnart, Nicolas Lindegger, Marco Mongillo, Peter J. Mohler, Andrew R. Marks. Phosphorylation of the ryanodine receptor mediates the cardiac fight or flight response in mice. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI32726
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