Mitochondrial dysfunction on sinoatrial node and pulmonary vein electrophysiological activities

Lin,Yung‑Kuo; Cheng,Chen‑Chuan; Tsai,Min‑Chien; Wu,Pei‑Yu; Chen,Yi‑Ann; Chen,Yao‑Chang; Chen,Shih‑Ann; Chen,Yi‑Jen

doi:10.3892/etm.2017.4285

Mitochondrial dysfunction on sinoatrial node and pulmonary vein electrophysiological activities

Authors:
- Yung‑Kuo Lin
- Chen‑Chuan Cheng
- Min‑Chien Tsai
- Pei‑Yu Wu
- Yi‑Ann Chen
- Yao‑Chang Chen
- Shih‑Ann Chen
- Yi‑Jen Chen
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Affiliations: Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan, R.O.C., Division of Cardiology, Chi‑Mei Medical Center, Tainan 710, Taiwan, R.O.C., Department of Biomedical Engineering and Graduate Institute of Physiology, National Defense Medical Center, Taipei 114, Taiwan, R.O.C., Division of Nephrology, Sijhih Cathay General Hospital, New Taipei 221, Taiwan, R.O.C., Division of Cardiology and Cardiovascular Research Center, Taipei Veterans General Hospitals, National Yang‑Ming University School of Medicine, Taipei 112, Taiwan, R.O.C.
Published online on: March 30, 2017 https://doi.org/10.3892/etm.2017.4285
Pages: 2486-2492

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Abstract

Atrial fibrillation (AF) is associated with mitochondrial dysfunction. Sinoatrial node (SAN) dysfunction increases arrhythmogenesis of pulmonary veins (PVs), which is the most important trigger of AF; however, it is not clear whether mitochondrial dysfunction differentially regulates electrical activity of SANs and PVs. In the present study, conventional microelectrodes were used to record the action potentials (APs) in isolated rabbit PVs, SANs, left atrium (LA) and right atrium (RA) before and after application of trifluorocarbonylcyanide phenylhydrazone (FCCP; a mitochondrial uncoupling agent) at 10, 100 and 300 nM. FCCP application at 100 and 300 nM decreased spontaneous rates in PVs and in SANs at 10, 100 and 300 nM. FCCP shortened the 20, 50 and 90% AP durations in the LA, and shortened only the 20% AP duration in the RA. FCCP caused a greater rate reduction in SANs than in PVs; however, in the presence of coenzyme-Q10 (10 µM), FCCP reduced the beating rate in PVs and SANs to a similar extent. In SAN‑PV preparations with intact electrical connections, FCCP (100 nM) application shifted the SAN‑PV electrical conduction into PV‑SAN conduction in 5 (62.5%) of 8 preparations. In conclusion, mitochondrial dysfunction modulates PV and SAN electrical activities, which may contribute to atrial arrhythmogenesis.

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