Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC160
Electrical remodeling of potassium currents in right atrial myocytes from sheep persistent atrial fibrillation model.
N. Doisne1, P. Holemans1, I. Lenaerts1, G. Antoons1, R. Willems1, K. R. Sipido1
1. Experimental Cardiology, KULeuven, Leuven, Belgium.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia observed in clinical practice. Persistent atrial fibrillation has been associated with structural and electrical remodeling. The objective of this study was to characterize the remodeling of potassium currents (especially the inward rectifier IK1, the transient outward Ito and the ultra-rapid delayed rectifier IKur) in a sheep model of persistent AF. We studied whole cell currents with the patch-clamp technique in right atrial myocytes isolated from 5 sheep with persistent AF, compared to 11 animals in sinus rhythm. AF animals were instrumented with an atrial and ventricular pacemaker using a transvenous approach. Pacemaker insertion at the shoulder was carried out under general anesthesia with isoflurane (1%) after pre-medication with ketamine (10 mg.kg-1) and xylazine (0.2 mg.kg-1) intramuscular. First of all, the density of the inward rectifier IK1 (considered as the Ba2+ 500µM sensitive current) was greater in AF animals (-3.37±0.34 pA/pF vs -6.1±0.59 pA/pF at -120mV, p<0.0001). The reversal potential and the potential at maximal density were not different between control and AF animals. We considered the ultra-rapid delayed rectifier current as the 4-AP 50µM sensitive current and the transient outward current as the 4-AP 5mM sensitive current. The density of the 4-AP 50µM sensitive current tended to be smaller in the AF group (0.92±0.14 pA/pF vs 0.52±0.12 pA/pF at +60mV, p=0.186), without any difference in the time constant of inactivation (241±43 msec vs 438±99 msec in SR and AF animals, respectively, NS). The density of the 4-AP 5mM sensitive current was significantly smaller in AF atrial cells (1.4±0.19 pA/pF vs 0.86±0.18 pA/pF at +60mV, p<0.05), without any difference in the time constant of inactivation (85±23 msec vs 68±12 msec in SR and AF atrial cells, respectively, NS). Persistent AF induces electrical remodeling of potassium currents in sheep. The ultra-rapid delayed rectifier and the transient outward currents are decreased, which can induce the occurrence of a triangular action potential (AP) which poorly adapts to heart rate changes. The inward rectifier current is increased, which shortens the AP, can induce a greater excitability of atrial cells and promote re-entry.
Where applicable, experiments conform with Society ethical requirements