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 (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_CaL 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 (1 μM) caused a further increase in 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 (n = 37 cells, 14 patients). This was less than that in the SR group (27 ± 4 ms; 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 I_CaL in human atrial cells. This reduced effect on 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.