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

详细信息    查看全文

• 作者：Calum J. Redpath ; Andrew C. Rankin ; Kathleen A. Kane and Antony J. Workman
• 关键词：Endothelin ; Atrium ; Myocyte ; Action potential ; Repolarisation ; Refractory period ; Abnormal automaticity ; Afterdepolarisation ; Calcium current ; Arrhythmia mechanisms ; Atrial fibrillation
• 刊名：Journal of Molecular and Cellular Cardiology
• 出版年：2006
• 出版时间：May 2006
• 年：2006
• 卷：40
• 期：5
• 页码：717-724
• 全文大小：542 K

文摘

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; 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 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.