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

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Redpath, Calum J. and Rankin, Andrew C. and Kane, Kathleen A. and Workman, Antony 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. ISSN 0022-2828 (https://doi.org/10.1016/j.yjmcc.2006.01.012)

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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 (ICaL) 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; P<0.05, n=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 (P<0.05). Each was abolished by ET-1 at 10 nM (P<0.05). ISO (0.05 μM) increased peak ICaL 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 ICaL. Chronic treatment of patients with a β-blocker did not significantly alter basal APD50 or ICaL, the increase in APD50 or ICaL 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 ICaL, 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.

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