Anti-adrenergic effects of endothelin on human atrial action potentials are potentially anti-arrhythmic

Redpath, C., Rankin, A.C., Kane, K.A. and Workman, A.J. (2006) Anti-adrenergic effects of endothelin on human atrial action potentials are potentially anti-arrhythmic. Journal of Molecular and Cellular Cardiology, 40(5), pp. 717-724. (doi: 10.1016/j.yjmcc.2006.01.012)

Abstract

Endothelin-1 (ET-1) is elevated in patients with atrial fibrillation (AF) and heart failure. We investigated effects of ET-1 on human atrial cellular electrophysiological measurements expected to influence the genesis and maintenance of AF. Action potential characteristics and L-type Ca²⁺ current (I_CaL) were recorded by whole cell patch clamp, in atrial isolated myocytes obtained from patients in sinus rhythm. Isoproterenol (ISO) at 0.05 μM prolonged the action potential duration at 50% repolarisation (APD₅₀: 54 ± 10 vs. 28 ± 5 ms; <i>P</i> < 0.05, <i>N</i> = 15 cells, 10 patients), but neither late repolarisation nor cellular effective refractory period (ERP) were affected. ET-1 (10 nM) reversed the effect of ISO on APD₅₀, and had no basal effect (in the absence of ISO) on repolarisation or ERP. During repetitive stimulation, ISO (0.05 μM) produced arrhythmic depolarisations (<i>P</i> < 0.05). Each was abolished by ET-1 at 10 nM (<i>P</i> < 0.05). ISO (0.05 μM) increased peak I_CaL from –5.5 ± 0.4 to –14.6 ± 0.9 pA/pF (P < 0.05; N = 79 cells, 34 patients). ET-1 (10 nM) reversed this effect by 98 ± 10% (P < 0.05), with no effect on basal I_CaL. Chronic treatment of patients with a β-blocker did not significantly alter basal APD50 or I_CaL, the increase in APD50 or I_CaL by 0.05 μM ISO, nor the subsequent reversal of this effect on APD50 by 10 nM ET-1. The marked anti-adrenergic effects of ET-1 on human atrial cellular action potential plateau, arrhythmic depolarisations and I_CaL, without affecting ERP and independently of β-blocker treatment, may be expected to contribute a potentially anti-arrhythmic influence in the atria of patients with AF and heart failure.

• Item Type: Articles
• Keywords: Endothelin; Atrium; Myocyte; Action potential; Repolarisation; Refractory period; Abnormal automaticity; Afterdepolarisation; Calcium current; Arrhythmia mechanisms; Atrial fibrillation
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Rankin, Professor Andrew and Workman, Dr Antony
• Authors: Redpath, C., Rankin, A.C., Kane, K.A., and Workman, A.J.
• Subjects: R Medicine > RC Internal medicine; Q Science > QP Physiology
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities
• Journal Name: Journal of Molecular and Cellular Cardiology
• Publisher: Elsevier
• ISSN: 0022-2828
• Copyright Holders: Copyright © 2006 Elsevier
• First Published: First published in Journal of Molecular and Cellular Cardiology 40(5):717-724
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher.