Background: We have previously demonstrated the presence of a novel time-dependent K+ current carried by Kir3 channels in dog atrium (IKH) and shown that it has properties of constitutively active acetylcholine-dependent current. IKH is highly sensitive to tertiapin-Q (TQ, IC50 ~10 nM), a highly-selective Kir3 blocker. The present study assessed the potential role of IKH in atrial tachycardia (AT)-remodeled canine left atrial (LA) preparations with the use of TQ as a probe. Methods: Dogs were subjected to 7-13 days of AT at 400 bpm. LA preparations were then coronary-perfused and studied intact in vitro or subjected to cardiomyocyte isolation. IKH was studied with patch clamp. Results: AT pacing increased IKH at -110 mV from -2.2짹0.6 pA/pF (control) to -3.8짹0.7 pA/pF (AT) in LA cardiomyocytes, and the 100 nM TQ-sensitive component increased from -1.7짹0.5 (control) to -2.8짹0.5 (AT) pA/pF. Prolonged atrial tachyarrhythmias could be induced with single extrastimuli at varying cycle lengths in AT-remodeled, but not control, preparations. In AT-remodeled preparations, mean tachyarrhythmia duration was 11602짹604 ms (n=81, 8 dogs), with a cycle length of 108짹0.3 ms. Tachyarrhythmia duration was decreased significantly by 100 nM TQ, to 520짹6 ms (n=66, 8 dogs, P<0.05), and tachyarrhythmia cycle length increased to 179짹 0.8 ms (P<0.001). In 2 cases, tachyarrhythmia lasted uninterrupted for >20 minutes: TQ administration terminated arrhythmia within 4 minutes in both. TQ prominently increased the duration of action potentials in AT-remodeled canine LA (Table). Conclusions: AT-remodeling prominently increases IKH and a highly-selective antagonist, TQ, prominently increases action potential duration and suppresses atrial tachyarrhythmias in AT-remodeled preparations. Inhibition of the constitutive acetylcholine-related K+-current IKH is a potentially interesting novel approach to the treatment of AF.