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 microM, 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.


CONCLUSIONS
Endothelin-1 may have an antiarrhythmic potential through its direct electrophysiological effects on the PV cardiomyocytes and its action on multiple ionic currents.
Udyavar
Ameya R
AR
School of Medicine, National Yang-Ming University, Cardiovascular Research Center, Veterans General Hospital-Taipei, Taipei, Taiwan.
Chen
Yao-Chang
YC
Chen
Yi-Jen
YJ
Cheng
Chen-Chuan
CC
Lin
Cheng-I
CI
Chen
Shih-Ann
SA
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D001683:Biological Clocks / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000008:administration & dosage*; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D011667:Pulmonary Veins / Q000187:drug effects / Q000503:physiopathology*; D011817:Rabbits
D000889:Anti-Arrhythmia Agents; D019332:Endothelin-1