Related Experiment Videos
Electrophysiological effects of endothelin-1 on canine myocardial cells
R Yorikane1, H Koike, S Miyake
1Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Insights
Endothelin-1 (ET-1) directly affects cardiac cells, prolonging action potential duration and causing early afterdepolarizations (EADs) in the right bundle branch. These findings suggest ET-1 contributes to arrhythmias through direct electrophysiological actions.
Area of Science:
- Cardiovascular Physiology
- Cardiac Electrophysiology
Background:
- Endothelin-1 (ET-1) is known to induce ventricular arrhythmias linked to myocardial ischemia.
- A direct arrhythmogenic role of ET-1 independent of ischemia requires investigation.
Purpose of the Study:
- To investigate the direct electrophysiological effects of Endothelin-1 (ET-1) on canine cardiac tissues.
- To determine if ET-1 can induce arrhythmias through mechanisms independent of myocardial ischemia.
Main Methods:
- Isolated canine cardiac tissues (right bundle branch, false tendon, ventricular muscle, atrial muscle) were used.
- Transmembrane potentials were recorded using conventional microelectrode techniques.
- Effects of ET-1 and Bay K 8644 (calcium channel agonist) were assessed, with interventions like nicardipine.
Main Results:
- ET-1 prolonged action potential duration (APD) in most tissues, except atrial muscle where it was shortened.
- Significant APD prolongation and early afterdepolarizations (EADs) were observed specifically in the right bundle branch.
- ET-1 suppressed spontaneous firing in the right bundle branch, unlike Bay K 8644.
Conclusions:
- ET-1 directly impacts cardiac electrophysiology, inducing EADs in the right bundle branch, suggesting a role for L-type calcium current.
- These direct electrophysiological effects, particularly EADs, contribute to ET-1-induced arrhythmias.
- The findings highlight a direct arrhythmogenic mechanism of ET-1 beyond its association with myocardial ischemia.
Abstract:
Endothelin-1 (ET-1) has been shown to induce severe ventricular arrhythmias associated with myocardial ischemia. However, ET-1 may have a direct arrhythmogenic action that is not related to myocardial ischemia. To examine this possibility, we studied the electrophysiological effects of ET-1 on cardiac tissues. The right bundle branch, false tendon, ventricular muscle, and atrial muscle were isolated from the dog, and transmembrane potentials were recorded by the conventional microelectrode technique. ET-1 prolonged the action potential duration (APD) in all of the tissues tested except in the atrial muscle, where the APD was shortened. Bay K 8644, a calcium channel agonist, prolonged the APD in all cardiac tissues. Spontaneous firing of the right bundle branch was suppressed by ET-1 but not Bay K 8644. The prolongation of the APD by ET-1 was far more marked in the right bundle branch than in other tissues, and it was followed by the development of early after depolarizations (EADs) only in the right bundle branch. The EADs induced by ET-1 or Bay K 8644 were abolished by nicardipine. These data suggest that L-type calcium current is involved in the genesis of EADs by ET-1, although other ionic mechanisms can not be ruled out. Since EADs underlie some types of arrhythmias, arrhythmias caused by ET-1 are at least partly attributable to the direct actions of the agent on myocardial cells.