title: 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-HT(4) 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 Ca(2+) current (I(CaL)), action potential duration (APD) and arrhythmic activity at 37 degrees C in enzymatically isolated atrial cells obtained from patients undergoing cardiac surgery, in SR or with chronic AF. In the AF group, 5-HT (10microM) 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 (1microM) 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 (APD(50)) 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 I(CaL) in human atrial cells. This reduced effect on I(CaL) was associated with a reduced APD(50) and arrhythmic activity with 5-HT. Thus, the potentially arrhythmogenic influence of 5-HT may be suppressed in AF-remodelled human atrium.
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK. d.pau@clinmed.gla.ac.uk
authors.forename: Davide
authors.initials: D
authors.lastname: Pau
authors.forename: Antony J
authors.initials: AJ
authors.lastname: Workman
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Kane
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Rankin
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000368:Aged; D001281:Atrial Fibrillation / Q000473:pathology / Q000503:physiopathology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D012701:Serotonin / Q000494:pharmacology*
chemical_list: D000319:Adrenergic beta-Antagonists; D020746:Calcium Channels, L-Type; D012701:Serotonin; D007545:Isoproterenol