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Progressive age-associated activation of JNK associates with conduction disruption in the aged atrium

Jones, Sandra A.; Lancaster, Matthew K.


Matthew K. Lancaster


Connexin43 (Cx43) is critical for maintaining electrical conduction across atrial muscle. During progressive ageing atrial conduction slows associating with increasing susceptibility to arrhythmias. Changes in Cx43 protein expression, or its phosphorylation status, can instigate changes in the conduction of the cardiac action potential. This study investigated whether increased levels of activated c-jun N-terminal kinase (JNK) is responsible for the decline of Cx43 during ageing. Right atria from guinea pigs aged between 1 day and 38 months of age were examined. The area of the intercalated disc increased with age concurrent with a 75% decline in C43 protein expression. An age-dependent increase in activated-JNK correlated with a rise in phosphorylated Cx43, but also slowing of action potential conduction velocity across the atria from 0.38 ± 0.01 m/s at 1 month of age to 0.30 ± 0.01 m/s at 38 months. The JNK activator anisomycin increased activated JNK in myocytes and reduced Cx43 protein expression simulating ageing. The JNK inhibitor SP600125, was found to eradicate almost all trace of Cx43 protein. We conclude that in vivo activation of JNK increases with age leading to the loss of Cx43 protein resulting in impaired conduction and contributing to the increasing risk of atrial arrhythmias with advancing age.


Jones, S. A., & Lancaster, M. K. (2015). Progressive age-associated activation of JNK associates with conduction disruption in the aged atrium. Mechanisms of ageing and development, 146-148, 72-80.

Acceptance Date May 1, 2015
Online Publication Date May 5, 2015
Publication Date 2015-02
Deposit Date May 26, 2015
Publicly Available Date Jul 18, 2018
Journal Mechanisms of ageing and development
Print ISSN 0047-6374
Electronic ISSN 1872-6216
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 146-148
Pages 72-80
Keywords Atria; Connexin43; Gap junction; Conduction velocity; JNK
Public URL
Publisher URL
Additional Information Copy of article first published in: Mechanisms of ageing and development, 2015, v.146


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Copyright Statement
This work is licensed under a Creative Commons Attribution 4.0 International License.

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