(Circulation. 1999;99:1898-1905.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Transient Outward Current, Ito1, Is Altered in Cardiac Memory
From the Departments of Physiology and Biophysics and Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, NY (H.Y., D.M., J.E.D., J.G., R.W., I.S.C.), and the Departments of Pharmacology and Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY (P.D., A.S., E.P.A., E.A.S., M.H., M.R.R.).
Correspondence to Michael R. Rosen, MD, Gustavus A. Pfeiffer Professor of Pharmacology, Professor of Pediatrics, College of Physicians and Surgeons of Columbia University, Department of Pharmacology, 630 W 168 St, PH 7West-321, New York, NY 10032. E-mail emf3{at}columbia.edu
Background—Cardiac memory refers to an altered T-wave morphology induced by ventricular pacing or arrhythmias that persist for variable intervals after resumption of sinus rhythm.
Methods and Results—We induced long-term cardiac memory (LTM) in conscious dogs by pacing the ventricles at 120 bpm for 3 weeks. ECGs were recorded daily for 1 hour, during which time pacing was discontinued. At terminal study, the heart was removed and the electrophysiology of left ventricular epicardial myocytes was investigated. Control (C) and LTM ECG did not differ, except for T-wave amplitude, which decreased from 0.12±0.18 to -0.34±0.21 mV (±SEM, P<0.05), and T-wave vector, which shifted from -37±12° to -143±4° (P<0.05). Epicardial action potentials revealed loss of the notch and lengthening of duration at 20 days (both P<0.05). Calcium-insensitive transient outward current (Ito) was investigated by whole-cell patch clamp. No difference in capacitance was seen in C and LTM myocytes. Ito activated on membrane depolarization to -25±1 mV in C and -7±1 mV (P<0.05) in LTM myocytes, indicating a positive voltage shift of activation. Ito density was reduced in LTM myocytes, and a decreased mRNA level for Kv4.3 was observed. Recovery of Ito from inactivation was significantly prolonged: it was 531±80 ms (n=10) in LTM and 27±6 ms (n=9) in C (P<0.05) at -65 mV.
Conclusions—Ito changes are associated with and can provide at least a partial explanation for action-potential and T-wave changes occurring with LTM.
Key Words: electrocardiography • ventricles • pacing • myocytes
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