Title
Adrenergic deficiency leads to impaired electrical conduction and increased arrhythmic potential in the embryonic mouse heart
Abbreviated Journal Title
Biochem. Biophys. Res. Commun.
Keywords
Adrenergic regulation; Arrhythmia; Cardiac development; Cardiac gap; junctions; Conduction velocity; PHENYLETHANOLAMINE N-METHYLTRANSFERASE; CARDIAC CONDUCTION; GAP-JUNCTIONS; RAT-HEART; CATECHOLAMINES; CONNEXIN43; EXPRESSION; SYSTEM; GENE; MICE; Biochemistry & Molecular Biology; Biophysics
Abstract
To determine if adrenergic hormones play a critical role in the functional development of the cardiac pacemaking and conduction system, we employed a mouse model where adrenergic hormone production was blocked due to targeted disruption of the dopamine beta-hydroxylase (Dbh) gene. Immunofluorescent histochemical evaluation of the major gap junction protein, connexin 43, revealed that its expression was substantially decreased in adrenergic-deficient (Dbh(-/-)) relative to adrenergic-competent (Dbh(+/+) and Dbh(+/-)) mouse hearts at embryonic day 10.5 (E10.5), whereas pacemaker and structural protein staining appeared similar. To evaluate cardiac electrical conduction in these hearts, we cultured them on microelectrode arrays (8 x 8,200 mu m apart). Our results show a significant slowing of atrioventricular conduction in adrenergic-deficient hearts compared to controls (31.4 +/- 6.4 vs. 15.4 +/- 1.7 ms, respectively, p < 0.05). To determine if the absence of adrenergic hormones affected heart rate and rhythm, mouse hearts from adrenergic-competent and deficient embryos were cultured ex vivo at E10.5, and heart rates were measured before and after challenge with the beta-adrenergic receptor agonist, isoproterenol (0.5 mu M). On average, all hearts showed increased heart rate responses following isoproterenol challenge, but a significant (p < 0.05) 225% increase in the arrhythmic index (AI) was observed only in adrenergic-deficient hearts. These results show that adrenergic hormones may influence heart development by stimulating connexin 43 expression, facilitating atrioventricular conduction, and helping to maintain cardiac rhythm during a critical phase of embryonic development. (C) 2012 Elsevier Inc. All rights reserved.
Journal Title
Biochemical and Biophysical Research Communications
Volume
423
Issue/Number
3
Publication Date
1-1-2012
Document Type
Article
Language
English
First Page
536
Last Page
541
WOS Identifier
ISSN
0006-291X
Recommended Citation
"Adrenergic deficiency leads to impaired electrical conduction and increased arrhythmic potential in the embryonic mouse heart" (2012). Faculty Bibliography 2010s. 2261.
https://stars.library.ucf.edu/facultybib2010/2261
Comments
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