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

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 287; no. 1; pp. H178 - H186
• Main Authors: Miyauchi, Yasushi, Fishbein, Michael C, Karagueuzian, Hrayr S
• Format: Journal Article
• Language: English
• Published: United States 01.07.2004
• Subjects: Action Potentials - drug effects; Animals; Anti-Arrhythmia Agents - pharmacology; Atrial Function; Atropine - pharmacology; Diastole; Electric Conductivity; Male; Myocytes, Cardiac - cytology; Propranolol - pharmacology; Pulmonary Veins - cytology; Pulmonary Veins - physiology; Rats; Rats, Inbred F344; Reaction Time - drug effects; Refractory Period, Electrophysiological
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00085.2004

Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, and 1 David Geffen School of Medicine, University of California-Los Angeles (UCLA), and 2 Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, California 90048 Submitted 29 January 2004 ; accepted in final form 27 February 2004 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°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 µM, n = 10) prevented, whereas propranolol (2 µM, 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. acetylcholine; reentry; dispersion of repolarization; arrhythmias Address for reprint requests and other correspondence: H. S. Karagueuzian, 8700 Beverly Blvd., Davis Research Bldg., Rm. 6066, Los Angeles, CA 90048 (E-mail: karagueuzian{at}cshs.org ).