Fields, L., Koschinski, A. and Zaccolo, M. (2016) Sustained exposure to catecholamines affects cAMP/PKA compartmentalised signalling in adult rat ventricular myocytes. Cellular Signalling, 28(7), pp. 725-732. (doi: 10.1016/j.cellsig.2015.10.003) (PMID:26475678) (PMCID:PMC4872538)
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Abstract
In the heart compartmentalisation of cAMP/protein kinase A (PKA) signalling is necessary to achieve a specific functional outcome in response to different hormonal stimuli. Chronic exposure to catecholamines is known to be detrimental to the heart and disrupted compartmentalisation of cAMP signalling has been associated to heart disease. However, in most cases it remains unclear whether altered local cAMP signalling is an adaptive response, a consequence of the disease or whether it contributes to the pathogenetic process. We have previously demonstrated that isoforms of PKA expressed in cardiac myocytes, PKA-I and PKA-II, localise to different subcellular compartments and are selectively activated by spatially confined pools of cAMP, resulting in phosphorylation of distinct downstream targets. Here we investigate cAMP signalling in an in vitro model of hypertrophy in primary adult rat ventricular myocytes. By using a real time imaging approach and targeted reporters we find that that sustained exposure to catecholamines can directly affect cAMP/PKA compartmentalisation. This appears to involve a complex mechanism including both changes in the subcellular localisation of individual phosphodiesterase (PDE) isoforms as well as the relocalisation of PKA isoforms. As a result, the preferential coupling of PKA subsets with different PDEs is altered resulting in a significant difference in the level of cAMP the kinase is exposed to, with potential impact on phosphorylation of downstream targets.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Zaccolo, Professor Manuela and Koschinski, Dr Andreas |
| Authors: | Fields, L., Koschinski, A., and Zaccolo, M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience |
| Journal Name: | Cellular Signalling |
| Publisher: | Elsevier |
| ISSN: | 0898-6568 |
| ISSN (Online): | 1873-3913 |
| Published Online: | 01 October 2015 |
| Copyright Holders: | Copyright © 2015 The Authors |
| First Published: | First published in Cellular Signalling 28(7):725-732 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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