The subcellular localisation of neuronal nitric oxide synthase determines the downstream effects of NO on myocardial function
العنوان: | The subcellular localisation of neuronal nitric oxide synthase determines the downstream effects of NO on myocardial function |
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المؤلفون: | Carnicer R, Suffredini S, Liu X, Reilly S, Jn, Simon, Nc, Surdo, Yh, Zhang, Ca, Lygate, keith channon, Casadei B |
المصدر: | Europe PubMed Central Cardiovascular Research |
سنة النشر: | 2017 |
مصطلحات موضوعية: | Cardiac Biology and Remodelling, inorganic chemicals, Excitation–contraction coupling, nervous system, Calcium channel, Neuronal NOS, cardiovascular system, Nitric oxide, Original Articles, Cardiomyocyte, musculoskeletal system, tissues |
الوصف: | Aim: In healthy hearts, the neuronal nitric oxide synthase (nNOS) is predominantly localised to the sarcoplasmic reticulum (SR), where it regulates the ryanodine receptor Ca2+ release channel (RyR2) and phospholamban (PLB) phosphorylation, and to a lesser extent to the sarcolemmal membrane where it inhibits the L-type Ca2+ current (ICa). However, in failing hearts, impaired relaxation and depressed inotropy are associated with a larger proportion of nNOS being localised to the sarcolemmal membrane. Whether there is a causal relationship between altered myocardial function and subcellular localisation of nNOS remains to be assessed. Methods and Results: Adenoviruses (AdV) encoding for a human nNOS.eGFP fusion protein or eGFP were injected into the left ventricle (LV) of nNOS-/- mice. nNOS.eGFP localised to the sarcolemmal and t-tubular membrane and immunoprecipitated with syntrophin and caveolin-3 but not with RyR2. Myocardial transduction of nNOS.eGFP resulted in a significantly increased NOS activity (10-fold, P |
تدمد: | 1755-3245 0008-6363 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::bb8e966024b41ec8618c27936357bf2a http://ora.ox.ac.uk/objects/uuid: |
حقوق: | OPEN |
رقم الأكسشن: | edsair.pmid.dedup....bb8e966024b41ec8618c27936357bf2a |
قاعدة البيانات: | OpenAIRE |
تدمد: | 17553245 00086363 |
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