Scn3b knockout mice exhibit abnormal sino-atrial and cardiac conduction properties
Aim: In contrast to extensive reports on the roles of Nav1.5 α‐subunits, there have been few studies associating the β‐subunits with cardiac arrhythmogenesis. We investigated the sino‐atrial and conduction properties in the hearts of Scn3b−/− mice. Methods: The following properties were compared i...
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Published in | Acta Physiologica Vol. 198; no. 1; pp. 47 - 59 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
01.01.2010
Wiley-Blackwell |
Subjects | |
Online Access | Get full text |
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Summary: | Aim: In contrast to extensive reports on the roles of Nav1.5 α‐subunits, there have been few studies associating the β‐subunits with cardiac arrhythmogenesis. We investigated the sino‐atrial and conduction properties in the hearts of Scn3b−/− mice.
Methods: The following properties were compared in the hearts of wild‐type (WT) and Scn3b−/− mice: (1) mRNA expression levels of Scn3b, Scn1b and Scn5a in atrial tissue. (2) Expression of the β3 protein in isolated cardiac myocytes. (3) Electrocardiographic recordings in intact anaesthetized preparations. (4) Bipolar electrogram recordings from the atria of spontaneously beating and electrically stimulated Langendorff‐perfused hearts.
Results: Scn3b mRNA was expressed in the atria of WT but not Scn3b−/− hearts. This was in contrast to similar expression levels of Scn1b and Scn5a mRNA. Immunofluorescence experiments confirmed that the β3 protein was expressed in WT and absent in Scn3b−/− cardiac myocytes. Lead I electrocardiograms from Scn3b−/− mice showed slower heart rates, longer P wave durations and prolonged PR intervals than WT hearts. Spontaneously beating Langendorff‐perfused Scn3b−/− hearts demonstrated both abnormal atrial electrophysiological properties and evidence of partial or complete dissociation of atrial and ventricular activity. Atrial burst pacing protocols induced atrial tachycardia and fibrillation in all Scn3b−/− but hardly any WT hearts. Scn3b−/− hearts also demonstrated significantly longer sinus node recovery times than WT hearts.
Conclusion: These findings demonstrate, for the first time, that a deficiency in Scn3b results in significant atrial electrophysiological and intracardiac conduction abnormalities, complementing the changes in ventricular electrophysiology reported on an earlier occasion. |
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Bibliography: | istex:90173BE2276CF96FAB201AD315E779B36B7A72D1 ArticleID:APHA2048 ark:/67375/WNG-Q8TGXXV0-R ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://www3.interscience.wiley.com/authorresources/onlineopen.html |
ISSN: | 1748-1708 1748-1716 |
DOI: | 10.1111/j.1748-1716.2009.02048.x |