Kir3-based inward rectifier potassium current: potential role in atrial tachycardia remodeling effects on atrial repolarization and arrhythmias.
BACKGROUND
We previously characterized a novel K+ current (IKH) with properties of constitutively active acetylcholine-related current in dog atrium. I(KH) is sensitive to tertiapin-Q (IC50 approximately 10 nmol/L), a highly selective Kir3 current blocker. This study assessed the role of IKH in atrial tachycardia (AT)-remodeled canine left atrium (LA) with the use of tertiapin-Q as a probe.


RESULTS
Dogs were subjected to 7 to 13 days of AT (400 bpm). Coronary-perfused LA preparations were studied intact or subjected to cardiomyocyte isolation. IKH was recorded with patch-clamp methods. AT pacing increased time-dependent hyperpolarization-activated current (IKH) at -110 mV from -1.8+/-0.3 (control) to -3.4+/-0.5 pA/pF (AT) and the 100-nmol/L tertiapin-sensitive component from -1.5+/-0.4 (control) to -3.3+/-0.6 pA/pF (AT). Prolonged atrial tachyarrhythmias could be induced with single extrastimuli in AT-remodeled, but not control, preparations, reflecting the atrial fibrillation-promoting effects of AT remodeling. In AT-remodeled preparations, tachyarrhythmia duration averaged 11.0+/-5.2 seconds, with a cycle length of 108+/-6 ms. Tertiapin-Q decreased tachyarrhythmia duration (to 0.6+/-0.1 second; P<0.001) and increased tachyarrhythmia cycle length (to 175+/-10 ms; P<0.001). Atrial action potential duration (APD) was increased 65+/-6% by tertiapin in AT-remodeled hearts versus 19+/-2% (P<0.001) in control. In 2 AT-remodeled preparations, tachyarrhythmia lasted uninterrupted for >20 minutes; tertiapin-Q slowed and then terminated arrhythmia in both. Tertiapin had no effect on left ventricular cardiomyocyte currents or APD.


CONCLUSIONS
AT remodeling increases IKH, and a highly selective Kir3 current antagonist, tertiapin-Q, increases APD and suppresses atrial tachyarrhythmias in AT-remodeled preparations without affecting ventricular electrophysiology. Constitutive acetylcholine-related K+ current contributes to AT-remodeling effects in dogs and is a potentially interesting antiarrhythmic target.
Kosin University College of Medicine, Busan, South Korea.
Tae-Joon
TJ
Cha
Joachim R
JR
Ehrlich
Denis
D
Chartier
Xiao-Yan
XY
Qi
Ling
L
Xiao
Stanley
S
Nattel
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D001281:Atrial Fibrillation / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D004594:Electrophysiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000502:physiology*; D006325:Heart Atria / Q000503:physiopathology; D013610:Tachycardia / Q000503:physiopathology*; D020257:Ventricular Remodeling
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels