title: The ultrarapid and the transient outward K(+) current in human atrial fibrillation. Their possible role in postoperative atrial fibrillation.
abstract: Atrial fibrillation (AF) causes distinct changes in atrial conduction, characterized as electrical remodeling. Experimental data on the possible significance of alterations of specific K(+)outward currents in this process are still limited in human AF. The ultra-rapid delayed rectifier current (I(Kur)) has not been studied in AF with respect to its sensitivity to 4-Aminopyridine (4-AP). To clarify the role of (1) the 4-AP sensitive I(Kur)current, compared to recordings without using 4-AP (I(Kur*)), and (2) the transient outward current (I(to)) in changes of atrial repolarization associated with AF, whole cell voltage-clamp recordings were obtained from atrial myocytes of patients undergoing elective cardiac surgery, with and without a history of atrial fibrillation (AF/non-AF). Further, a possible relation between experimental data and postoperative AF was studied. In AF patients, I(Kur*)was reduced by 40% [5.00+/-0.32 pA/pF (non-AF) and 2.91+/-0. 45 pA/pF (AF) at +50 mV, P<0.0001, n=22/11], I(Kur)by 55% [3.81+/-0. 30 pA/pF (non-AF) and 1.71+/-0.20 pA/pF (AF) at +50 mV, P<0.0001, n=22/11]. The mean amplitude of I(Kur)was significantly smaller than I(Kur*). Consistently, I(to)was reduced by 44% [11.57+/-0.77 pA/pF (non-AF) and 6.51+/-1.31 pA/pF (AF), P<0.01, n=25/11]. In 48% of non-AF patients, postoperative AF was detected. The corresponding voltage-clamp recordings showed a trend to reduced I(Kur*)and I(Kur)currents, although it did not reach statistical significance. The consistent reduction of all three K(+)currents investigated due to the presence of AF indicates an important association of abnormalities in cellular repolarization with the onset and the self-sustaining nature of human AF.
authors.affiliation: Department of Medicine III, University of Cologne, Joseph-Stelzmann Strasse 9, Cologne, 50924, Germany.
authors.forename: M C
authors.initials: MC
authors.lastname: Brandt
authors.forename: L
authors.initials: L
authors.lastname: Priebe
authors.forename: T
authors.initials: T
authors.lastname: Böhle
authors.forename: M
authors.initials: M
authors.lastname: Südkamp
authors.forename: D J
authors.initials: DJ
authors.lastname: Beuckelmann
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000368:Aged; D001281:Atrial Fibrillation / Q000378:metabolism*; D002478:Cells, Cultured; D003327:Coronary Disease / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism* / Q000502:physiology; D015221:Potassium Channels / Q000378:metabolism
chemical_list: D015221:Potassium Channels; D015761:4-Aminopyridine; D011188:Potassium