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

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 (ICaL), 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 (10μM) produced an increase in ICaL of 115±21% above control (n=10 cells, 6 patients) that was significantly smaller than that in the SR group (232±33%; p<0.05; n=27 cells, 12 patients). Subsequent co-application of isoproterenol (1μM) caused a further increase in ICaL 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±3ms by 5-HT in the AF group (n=37 cells, 14 patients). This was less than that in the SR group (27±4ms; p<0.05; n=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 ICaL in human atrial cells. This reduced effect on ICaL 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.