Endothelin-1 Modulates the Arrhythmogenic Activity of Pulmonary Veins

Objective: Endothelin‐1 has important cardiovascular effects and is activated during atrial fibrillation. Pulmonary veins (PVs) play a critical role in the pathophysiology of atrial fibrillation. The aim of this study was to evaluate whether endothelin‐1 affects PV arrhythmogenic activity. Methods: Conventional microelectrodes were used to record the action potentials (APs) and contractility in isolated rabbit PV tissue specimens before and after the administration of endothelin‐1 (0.1, 1, 10 nM). The ionic currents of isolated PV cardiomyocytes were investigated before and after the administration of endothelin‐1 (10 nM) through whole‐cell patch clamps. Results: In the tissue preparation, endothelin‐1 (1, 10 nM) concentration dependently shortened the AP duration and decreased the PV firing rates. Endothelin‐1 (10 nM) decreased the resting membrane potential. Endothelin‐1 (0.1, 1, 10 nM) decreased the contractility and increased the resting diastolic tension. In single PV cardiomyocytes, endothelin‐1 (10 nM) decreased the PV firing rates from 2.7 ± 1.0 Hz to 0.8 ± 0.5 Hz (n = 16). BQ‐485 (100 μM, endothelin‐1 type A receptor blocker) reversed and prevented the chrono‐inhibitory effects of endothelin‐1 (10 nM). Endothelin‐1 (10 nM) reduced the L‐type calcium currents, transient outward currents, delayed rectifier currents, transient inward currents, and sodium–calcium exchanger currents in the PV cardiomyocytes with and without pacemaker activity. Endothelin‐1 (10 nM) increased the inward rectifier potassium current, hyperpolarization‐induced pacemaker current, and the sustained outward potassium current in PV cardiomyocytes with and without pacemaker activity. Conclusion: Endothelin‐1 may have an antiarrhythmic potential through its direct electrophysiological effects on the PV cardiomyocytes and its action on multiple ionic currents.