The ultrarapid and the transient outward K(+) current in human atrial fibrillation. Their possible role in postoperative atrial fibrillation.
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.
Brandt
M C
MC
Department of Medicine III, University of Cologne, Joseph-Stelzmann Strasse 9, Cologne, 50924, Germany.
Priebe
L
L
Böhle
T
T
Südkamp
M
M
Beuckelmann
D J
DJ
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
D015221:Potassium Channels; D015761:4-Aminopyridine; D011188:Potassium