Nitric oxide (NO) is known to modulate calcium handling and cellular signaling in the myocardium, but key targets for NO in the heart remain unidentified. Recent reports have implicated that NO can activate calcium/calmodulin (Ca2+/CaM) dependent protein kinase II (CaMKII) in neurons and heart. Here, we use our novel sensor of CaMKII activation, Camui, to monitor changes in conformation and activation of cardiac CaMKII (CaMKIIδ) activity after treatment with the NO donor S-nitrosoglutathione (GSNO). We demonstrate that exposure to NO after Ca2+/CaM binding to CaMKIIδ results in autonomous kinase activation, which is abolished by mutation of the C290 site. However, exposure of CaMKIIδ to GSNO prior to Ca2+/CaM exposure strongly suppresses kinase activation and conformational change by Ca2+/CaM. This NO-induced inhibition was ablated by mutation of the C273 site. We found parallel effects of GSNO on CaM/CaMKIIδ binding and CaMKIIδ-dependent ryanodine receptor activation in adult cardiac myocytes. We conclude that NO can play a dual role in regulating cardiac CaMKIIδ activity.
Pharmacology, Toxicology and Pharmaceutical Science
2
4%
Engineering
2
4%
Other
3
6%
Unknown
19
36%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 July 2016.
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#17,302,400
of 25,394,764 outputs
Outputs from Journal of Biological Chemistry
#76,113
of 85,270 outputs
Outputs of similar age
#167,512
of 279,063 outputs
Outputs of similar age from Journal of Biological Chemistry
#280
of 468 outputs
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