Electrophysiological and arrhythmogenic effects of 5-hydroxytryptamine on human atrial cells are reduced in atrial fibrillation

Pau, D., Workman, A.J., Kane, K.A. and Rankin, A.C. (2007) Electrophysiological and arrhythmogenic effects of 5-hydroxytryptamine on human atrial cells are reduced in atrial fibrillation. Journal of Molecular and Cellular Cardiology, 42(1), pp. 54-62. (doi: 10.1016/j.yjmcc.2006.08.007)

Abstract

5-Hydroxytryptamine (5-HT) is proarrhythmic in atrial cells from patients in sinus rhythm (SR) via activation of 5-HT₄ receptors, but its effects in atrial cells from patients with atrial fibrillation (AF) are unknown. The whole-cell perforated patch-clamp technique was used to record L-type Ca²⁺ current (<i>I</i>_CaL), action potential duration (APD) and arrhythmic activity at 37 °C in enzymatically isolated atrial cells obtained from patients undergoing cardiac surgery, in SR or with chronic AF. In the AF group, 5-HT (10 μM) produced an increase in <i>I</i>_CaL of 115 ± 21% above control (<i>n</i> = 10 cells, 6 patients) that was significantly smaller than that in the SR group (232 ± 33%; <i>p</i> 0.05; <i>n</i> = 27 cells, 12 patients). Subsequent co-application of isoproterenol (1 μM) caused a further increase in <i>I</i>_CaL in the AF group (by 256 ± 94%) that was greater than that in the SR group (22 ± 6%; p < 0.05). The APD at 50% repolarisation (APD₅₀) was prolonged by 14 ± 3 ms by 5-HT in the AF group (<i>n</i> = 37 cells, 14 patients). This was less than that in the SR group (27 ± 4 ms; <i>p</i> < 0.05; <i>n</i> = 58 cells, 24 patients). Arrhythmic activity in response to 5-HT was observed in 22% of cells in the SR group, but none was observed in the AF group (p < 0.05). Atrial fibrillation was associated with reduced effects of 5-HT, but not of isoproterenol, on <i>I</i>_CaL in human atrial cells. This reduced effect on <i>I</i>_CaL was associated with a reduced APD₅₀ and arrhythmic activity with 5-HT. Thus, the potentially arrhythmogenic influence of 5-HT may be suppressed in AF-remodelled human atrium.

• Item Type: Articles
• Keywords: Patch-clamp; Myocytes; Atrial fibrillation; L-type calcium current; Action potentials; 5-HT; Isoproterenol
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Rankin, Professor Andrew and Workman, Dr Antony and Pau, Dr Davide
• Authors: Pau, D., Workman, A.J., Kane, K.A., and Rankin, A.C.
• Subjects: R Medicine > RC Internal medicine
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journal of Molecular and Cellular Cardiology
• Publisher: Elsevier
• ISSN: 0022-2828
• Copyright Holders: Copyright © 2007 Elsevier
• First Published: First published in Journal of Molecular and Cellular Cardiology 42(1):54-62
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher

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