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Cited by 480Nitric Oxide and Endothelin EffectsCardiac electrophysiology and arrhythmiasIon channel regulation and function

The DOI matches its Crossref record; 43 of the 44 references it cites were found in a registry or an index.

Nitric oxide synthase in cardiac sarcoplasmic reticulum

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Xu, Kai Y., Huso, David L., Dawson, Ted M., Bredt, David S., Becker, Lewis C.·1999·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.96.2.657PMC PMC15192
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Abstract

NO ⋅ is a free radical that modulates heart function and metabolism. We report that a neuronal-type NO synthase (NOS) is located on cardiac sarcoplasmic reticulum (SR) membrane vesicles and that endogenous NO ⋅ produced by SR-associated NOS inhibits SR Ca 2+ uptake. Ca 2+ -dependent biochemical conversion of l -arginine to l -citrulline was observed from isolated rabbit cardiac SR vesicles in the presence of NOS substrates and cofactors. Endogenous NO ⋅ was generated from the vesicles and detected by electron paramagnetic resonance spin-trapping measurements. Immunoelectron microscopy demonstrated labeling of cardiac SR vesicles by using anti-neuronal NOS (nNOS), but not anti-endothelial NOS (eNOS) or anti-inducible NOS (iNOS) antibodies, whereas skeletal muscle SR vesicles had no nNOS immunoreactivity. The nNOS immunoreactivity also displayed a pattern consistent with SR localization in confocal micrographs of sections of human myocardium. Western blotting demonstrated that cardiac SR NOS is larger than brain NOS (160 vs. 155 kDa). No immunodetection was observed in cardiac SR vesicles from nNOS knockout mice or with an anti-nNOSμ antibody, suggesting the possibility of a new nNOS-type isoform. 45 Ca uptake by cardiac SR vesicles, catalyzed by Ca 2+ -ATPase, was inhibited by NO ⋅ produced endogenously from cardiac SR NOS, and 7-nitroindazole, a selective nNOS inhibitor, completely prevented this inhibition. These results suggest that a cardiac muscle nNOS isoform is located on SR of cardiac myocytes, where it may respond to intracellular Ca 2+ concentration and modulate SR Ca 2+ ion active transport in the heart.

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  1. L J Ignarro Kidney Int Suppl 55, S2–S5 (1996).
  2. A J Brady, J B Warren, P A Poole-Wilson, T J Williams, S E Harding Am J Physiol 265, H176–H182 (1993).

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Metadata

Authors
Xu, K. Y., Huso, D. L., Dawson, T. M., Bredt, D. S., & Becker, L. C.
Affiliations
Johns Hopkins University (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1999-01-19
Volume
96
Issue
2
Pages
657-662
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.96.2.657
PMC
PMC15192
OpenAlex
W2058520514
Cited by
480
References
44
Citations by year
2026: 4 · 2025: 6 · 2024: 3 · 2023: 6 · 2022: 7 · 2021: 7 · 2020: 10 · 2019: 3 · 2018: 15 · 2017: 16 · 2016: 9 · 2015: 14 · 2014: 15 · 2013: 19 · 2012: 15
FWCI
13.78
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01hl033360-12)
  • National Heart, Lung, and Blood Institute (P50HL52315, R29HL052175, P50HL052315, HL33360, HL52175)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
nitric oxide synthase, neuronal nitric oxide synthase, cardiac sarcoplasmic reticulum, sarcoplasmic reticulum vesicles, nitric oxide, sarcoplasmic reticulum calcium uptake, Ca2+-ATPase, L-arginine to L-citrulline conversion, 7-nitroindazole, myocardium, intracellular calcium signaling
MeSH terms
Calcium-Transporting ATPases, Animals, Calcium, Electron Spin Resonance Spectroscopy, Enzyme Inhibitors, Immunohistochemistry, Myocardium, Nitric Oxide, Rabbits, Sarcoplasmic Reticulum, Microscopy, Confocal, Nitric Oxide Synthase

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