Electrical current-induced atrial and pulmonary vein action potential duration shortening and repetitive activity

Abstract

The influence of threshold electrical currents (EC) during regular drive on pulmonary vein (PV) and atrial myocardial cell action potential (AP) duration (APD) is unknown. We determined the effects of EC on cellular APD of PV, atria, and ventricles in isolated perfused and superfused male rat hearts (Fisher-344 strain, 3-4 mo old) at 37 degrees C (n = 14). We determined APD changes caused by subthreshold and threshold EC synchronized with a distant pacing electrode and delivered nearby cells from which transmembrane APs were recorded with a glass microelectrode. Progressive APD shortening (P < 0.001) and membrane hyperpolarization (P < 0.05) developed over a 20-s interval in the PV and atrial cells when the EC was delivered at <2 mm but not at >4 mm from the microelectrode. No such effects were seen in ventricular muscle cells. APD fully recovered 25 s after the cessation of EC application. Premature stimuli applied during EC-induced shortening of the APD caused rapid repetitive PV and atrial activity lasting two to five beats. Atropine (2 microM, n = 10) prevented, whereas propranolol (2 microM, n = 5) had no effect, on EC-induced APD shortening or repetitive activity. We conclude that EC shortens the APD and hyperpolarizes the membrane by local release of acetylcholine and causes the steep repolarization gradient in the vicinity of the current source leading to repetitive activity in atrial and PV cells during premature stimulation.

Mechanisms of atrial fibrillation termination by rapidly unbinding Na+ channel blockers: insights from mathematical models and experimental correlates

“…ACh activates I K(ACh) and thereby decreases the refractory period and hyperpolarizes the cell membrane (25). Such effects accelerate reentrant rotors maintaining AF and increase their angular velocity (30).…”

Ectopic activity in the rat pulmonary vein can arise from simultaneous activation of α1‐ and β1‐adrenoceptors

“…Despite many investigations, the mechanism generating focal activity in the pulmonary veins remains unknown (see Nattel, 2002 ; Page and Roden, 2005 for reviews). Most studies have concentrated upon pathological alterations to the electrophysiology of cardiac muscle cells in the pulmonary vein, including the possibility of delays in action potential conduction ( Chen et al ., 2000 ; Verheule et al ., 2002 ), alterations of action potential duration and effective refractory period ( Chen et al ., 2001 ; Jalife et al ., 2002 ; Scherlag et al ., 2002 ), high‐frequency firing and cellular Ca 2+ overload causing early after depolarizations ( Schauerte et al ., 2001 ; Miyauchi et al ., 2004 ; Patterson et al ., 2005 ), alterations in ion channels that might cause abnormal automaticity ( Bosch and Nattel, 2002 ; Khan, 2004 ; Melnyk et al ., 2005 ), and finally, automatism resulting from the activity of nodal myocytes in the pulmonary vein ( Masani, 1986 ; Chen and Yeh, 2003 ; Perez‐Lugones et al ., 2003 ).…”

Comparison of Ca2+-handling properties of canine pulmonary vein and left atrial cardiomyocytes

“…Chen et al (5)(6)(7)(8) found myocytes exhibiting automaticity in PV sleeves, with action potentials (APs) resembling those found in the sinoatrial node, but several other groups failed to find such automaticity under physiological conditions in tissue preparations (1,9,15,16,22,38). Reentry, the second mechanism, has been observed to occur in normal canine PVs (1) and apparently in PVs of patients with AF (20).…”