Reference : Neuronal nitric oxide synthase signaling in the heart is regulated by the sarcolemmal...
Scientific journals : Article
Human health sciences : Cardiovascular & respiratory systems
http://hdl.handle.net/10993/18340
Neuronal nitric oxide synthase signaling in the heart is regulated by the sarcolemmal calcium pump 4b.
English
Oceandy, Delvac [> >]
Cartwright, Elizabeth J. [> >]
Emerson, Michael [> >]
Prehar, Sukhpal [> >]
Baudoin, Florence M. [> >]
Zi, Min [> >]
Alatwi, Nasser [> >]
Venetucci, Luigi [> >]
Schuh, Kai [> >]
Williams, Judith C. [> >]
Armesilla, Angel L. [> >]
Neyses, Ludwig mailto [University of Luxembourg > Research Office]
2007
Circulation
115
4
483-92
Yes (verified by ORBilu)
International
0009-7322
1524-4539
United States
[en] Adrenergic beta-Agonists/pharmacology ; Animals ; Calcium/metabolism ; Calcium Channels, L-Type/metabolism ; Female ; Gene Expression ; Heart/physiology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Myocardial Contraction/physiology ; Myocardium/enzymology ; Nitric Oxide Synthase Type I/metabolism ; Plasma Membrane Calcium-Transporting ATPases/genetics/metabolism ; Receptors, Adrenergic, beta/metabolism ; Sarcolemma/enzymology ; Signal Transduction/physiology
[en] BACKGROUND: Neuronal nitric oxide synthase (nNOS) has recently been shown to be a major regulator of cardiac contractility. In a cellular system, we have previously shown that nNOS is regulated by the isoform 4b of plasma membrane calcium/calmodulin-dependent ATPase (PMCA4b) through direct interaction mediated by a PDZ domain (PSD 95, Drosophilia Discs large protein and Zona occludens-1) on nNOS and a cognate ligand on PMCA4b. It remains unknown, however, whether this interaction has physiological relevance in the heart in vivo. METHODS AND RESULTS: We generated 2 strains of transgenic mice overexpressing either human PMCA4b or PMCA ct120 in the heart. PMCA ct120 is a highly active mutant form of the pump that does not interact with or modulate nNOS function. Calcium was extruded normally from PMCA4b-overexpressing cardiomyocytes, but in vivo, overexpression of PMCA4b reduced the beta-adrenergic contractile response. This attenuated response was not observed in ct120 transgenic mice. Treatment with a specific nNOS inhibitor (N omega-propyl-L-arginine) reduced the beta-adrenergic response in wild-type and ct120 transgenic mice to levels comparable to those of PMCA4b transgenic animals. No differences in lusitropic response were observed in either transgenic strain compared with wild-type littermates. CONCLUSIONS: These data demonstrate the physiological relevance of the interaction between PMCA4b and nNOS and suggests its signaling role in the heart.
http://hdl.handle.net/10993/18340
10.1161/CIRCULATIONAHA.106.643791
http://circ.ahajournals.org/content/115/4/483.long

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