Ionic mechanisms of electrical remodeling in human atrial fibrillation.
OBJECTIVE
Atrial fibrillation (AF) is associated with a decrease in atrial ERP and ERP adaptation to rate as well as changes in atrial conduction velocity. The cellular changes in repolarization and the underlying ionic mechanisms in human AF are only poorly understood.


METHODS
Action potentials (AP) and ionic currents were studied with the patch clamp technique in single atrial myocytes from patients in chronic AF and compared to those from patients in stable sinus rhythm (SR).


RESULTS
The presence of AF was associated with a marked shortening of the AP duration and a decreased rate response of atrial repolarization. L-type calcium current (ICa,L) and the transient outward current (Ito) were both reduced about 70% in AF, whereas an increased steady-state outward current was detectable at test potentials between -30 and 0 mV. The inward rectifier potassium current (IKI) and the acetylcholine-activated potassium current (IKACh) were increased in AF at hyperpolarizing potentials. Voltage-dependent inactivation of the fast sodium current (INa) was shifted to more positive voltages in AF.


CONCLUSIONS
AF in humans leads to important changes in atrial potassium and calcium currents that likely contribute to the decrease in APD and APD rate adaptation. These changes contribute to electrical remodeling in AF and are therefore important factors for the perpetuation of the arrhythmia.
Bosch
R F
RF
Department of Cardiology, University of Tübingen, Germany. ralph.bosch@uni-tuebingen.de
Zeng
X
X
Grammer
J B
JB
Popovic
K
K
Mewis
C
C
Kühlkamp
V
V
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials; D000368:Aged; D020517:Atrial Appendage / Q000503:physiopathology*; D001281:Atrial Fibrillation / Q000503:physiopathology*; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D007473:Ion Channels; D008297:Male; D008875:Middle Aged; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects; D015222:Sodium Channels
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels; D000109:Acetylcholine