Mitochondrial dysfunction on sinoatrial node and pulmonary vein electrophysiological activities

Area of Science:

• Cardiovascular Physiology
• Mitochondrial Biology
• Cardiac Electrophysiology

Background:

• Atrial fibrillation (AF) is linked to mitochondrial dysfunction.
• Sinoatrial node (SAN) dysfunction and pulmonary vein (PV) arrhythmogenesis are key AF triggers.
• Differential regulation of SAN and PV electrical activity by mitochondrial dysfunction is unclear.

Purpose of the Study:

• To investigate how mitochondrial dysfunction differentially affects the electrical activity of SANs and PVs.
• To explore the role of mitochondrial uncoupling in modulating cardiac electrical conduction and arrhythmogenesis.

Main Methods:

• Conventional microelectrodes recorded action potentials (APs) in isolated rabbit PVs, SANs, left atrium (LA), and right atrium (RA).
• Trifluorocarbonylcyanide phenylhydrazone (FCCP), a mitochondrial uncoupler, was applied at varying concentrations (10, 100, 300 nM).
• Experiments included SAN-PV preparations to assess electrical conduction changes.

Main Results:

• FCCP decreased spontaneous rates in PVs and SANs, with a greater rate reduction observed in SANs.
• FCCP shortened AP durations in the LA and RA, with varying effects depending on the specific percentage of AP duration.
• Coenzyme-Q10 mitigated the differential rate reduction by FCCP in PVs and SANs.
• FCCP application shifted SAN-PV electrical conduction towards PV-SAN conduction in a majority of preparations.

Conclusions:

• Mitochondrial dysfunction significantly modulates the electrical activities of both PVs and SANs.
• Altered electrical conduction patterns, shifting from SAN-PV to PV-SAN, were observed under mitochondrial stress.
• These modulations in electrical activity by mitochondrial dysfunction may contribute to the development of atrial arrhythmogenesis.