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Wolverhampton Intellectual Repository and E-Theses > Research Institutes > Research Institute in Healthcare Science > Molecular Pharmacology Research Group > Neuronal Nitric Oxide Synthase Signaling in the Heart Is Regulated by the Sarcolemmal Calcium Pump 4b.

Please use this identifier to cite or link to this item: http://hdl.handle.net/2436/15807
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Title: Neuronal Nitric Oxide Synthase Signaling in the Heart Is Regulated by the Sarcolemmal Calcium Pump 4b.
Authors: 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 Luis
Neyses, Ludwig
Citation: Circulation, 115: 483-492.
Publisher: American Heart Association
Issue Date: 2007
URI: http://hdl.handle.net/2436/15807
DOI: 10.1161/CIRCULATIONAHA.106.643791
PubMed ID: 17242280
Additional Links: http://circ.ahajournals.org/cgi/content/abstract/115/4/483
Abstract: 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 (Nomega-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.
Type: Article
Language: en
Description: Metadata only
Keywords: Neuronal nitric oxide synthase
nNOS
Signal Transduction
Calcium
Cardiac contractility
ISSN: 1524-4539
Appears in Collections: Molecular Pharmacology Research Group

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