期刊
MECHANISMS OF AGEING AND DEVELOPMENT
卷 146, 期 -, 页码 72-80出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2015.05.001
关键词
Atria; Connexin43; Gap junction; Conduction velocity; JNK
资金
- British Heart Foundation [PG/11/15/28775]
- British Heart Foundation [PG/11/15/28775] Funding Source: researchfish
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. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.
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