Title

Adrenergic Deficiency Leads To Impaired Electrical Conduction And Increased Arrhythmic Potential In The Embryonic Mouse Heart

Keywords

Adrenergic regulation; Arrhythmia; Cardiac development; Cardiac gap junctions; Conduction velocity

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 β-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 (8×8, 200μm apart). Our results show a significant slowing of atrioventricular conduction in adrenergic-deficient hearts compared to controls (31.4±6.4 vs. 15.4±1.7ms, 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 β-adrenergic receptor agonist, isoproterenol (0.5μM). 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. © 2012 Elsevier Inc.

Publication Date

7-6-2012

Publication Title

Biochemical and Biophysical Research Communications

Volume

423

Issue

3

Number of Pages

536-541

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1016/j.bbrc.2012.05.163

Socpus ID

84863326613 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84863326613

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