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Proarrhythmic effect of sustained EPAC activation on TRPC3/4 in rat ventricular cardiomyocytes.
- Source :
-
Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 2015 Oct; Vol. 87, pp. 74-8. Date of Electronic Publication: 2015 Jul 26. - Publication Year :
- 2015
-
Abstract
- The Exchange Protein directly Activated by cAMP (EPAC) participates to the pathological signaling of cardiac hypertrophy and heart failure, in which the role of Ca(2+) entry through the Transient Receptor Potential Canonical (TRPC) channels begin to be appreciated. Here we studied whether EPAC activation could influence the activity and/or expression of TRPC channels in cardiac myocytes. In adult rat ventricular myocytes treated for 4 to 6h with the selective EPAC activator, 8-pCPT (10μM), we observed by Fluo-3 confocal fluorescence a Store-Operated Ca(2+) Entry (SOCE) like-activity, which was blunted by co-incubation with EPAC inhibitors (ESI-05 and CE3F4 at 10 μM). This SOCE-like activity, which was very small in control incubated cells, was sensitive to 30-μM SKF-96365. Molecular screening showed a specific upregulation of TRPC3 and C4 protein isoforms after 8-pCPT treatment. Moreover, sustained EPAC activation favored proarrhythmic Ca(2+) waves, which were reduced either by co-incubation with EPAC inhibitors or bath perfusion with TRPC inhibitors. Our study provides the first evidence that sustained selective EPAC activation leads to an increase in TRPC3 and C4 protein expression and induces a proarrhythmic SOCE-like activity in adult rat ventricular cardiomyocytes, which might be of importance during the development of cardiac diseases.<br /> (Copyright © 2015. Published by Elsevier Ltd.)
- Subjects :
- Animals
Benzene Derivatives administration & dosage
Calcium metabolism
Calcium Signaling drug effects
Cardiomegaly drug therapy
Cardiomegaly pathology
Complement C4 genetics
Cyclic AMP metabolism
Cyclic GMP administration & dosage
Cyclic GMP analogs & derivatives
Guanine Nucleotide Exchange Factors genetics
Heart Ventricles metabolism
Heart Ventricles pathology
Humans
Myocytes, Cardiac drug effects
Myocytes, Cardiac pathology
Quinolines administration & dosage
Rats
Sulfones administration & dosage
TRPC Cation Channels antagonists & inhibitors
Thionucleotides administration & dosage
Cardiomegaly genetics
Complement C4 biosynthesis
Guanine Nucleotide Exchange Factors biosynthesis
Myocytes, Cardiac metabolism
TRPC Cation Channels genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1095-8584
- Volume :
- 87
- Database :
- MEDLINE
- Journal :
- Journal of molecular and cellular cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 26219954
- Full Text :
- https://doi.org/10.1016/j.yjmcc.2015.07.002