Eur Rev Med Pharmacol Sci 2019; 23 (5): 2200-2207

DOI: 10.26355/eurrev_201903_17267

Exchange-protein activated by cAMP (EPAC) regulates L-type calcium channel in atrial fibrillation of heart failure model

M.-X. Zhang, J.-K. Zheng, W.-W. Wang, F.-Q. Kong, X.-X. Wu, J.-K. Jiang, J.-X. Pan

Department of Cardiovascular Medicine, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, China. 138684117@qq.com


OBJECTIVE: Both atrial fibrillation (AF) and heart failure (HF) are increasingly prevalent and related to high hospitalization rate and mortality. AF is a cause as well as a consequence of HF, with complicated interactions resulting in impairment of cardiac systolic and diastolic function. Conversely, the complex structural and neurohormonal alterations in HF contribute to the occurrence and development of AF. However, the molecular mechanism remains unclear. This study aims to explore the effect of Exchange-protein activated by cAMP 1 (EPAC1) on AF in isoproterenol (ISO)-induced HF and the potential molecular mechanism.

MATERIALS AND METHODS: Mice and cultured isolated adult cardiomyocytes were treated with ISO and or not EPAC1 inhibitor CE3F4. Programmed electrical stimulation (PES) was performed to induce AF. EPAC1 expression was determined by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and Western blot. Cellular electrophysiology was examined by whole cell patch clamp.

RESULTS: Both mRNA and protein levels of EPAC1 were upregulated in HF mice. ISO increased the AF susceptibility, and the negative effect was deteriorated by CE3F4. ISO mediated high AF susceptibility of HF via prolonging action potential and exciting L-type calcium channel (LTCC). These could also be reversed by CE3F4 treatment.

CONCLUSIONS: EPAC1 increased the AF susceptibility in ISO-induced HF mouse model via alternating LTCC.

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M.-X. Zhang, J.-K. Zheng, W.-W. Wang, F.-Q. Kong, X.-X. Wu, J.-K. Jiang, J.-X. Pan
Exchange-protein activated by cAMP (EPAC) regulates L-type calcium channel in atrial fibrillation of heart failure model

Eur Rev Med Pharmacol Sci
Year: 2019
Vol. 23 - N. 5
Pages: 2200-2207
DOI: 10.26355/eurrev_201903_17267