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(Circulation. 2003;107:2844.)
© 2003 American Heart Association, Inc.

Basic Science Reports

Role of L-Type Calcium Channels in Pacing-Induced Short-Term and Long-Term Cardiac Memory in Canine Heart

Alexei N. Plotnikov, MD^*; Hangang Yu, PhD^*; J. Christoph Geller, MD^*; Ravil Z. Gainullin, PhD; Parag Chandra, MBBS; Kornelis W. Patberg, MD; Steven Friezema, MD; Peter Danilo, Jr, PhD; Ira S. Cohen, MD, PhD; Steven J. Feinmark, PhD; Michael R. Rosen, MD

From the Center for Molecular Therapeutics, Departments of Pharmacology and Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY (A.N.P., R.Z.G., P.C., K.W.P., S.F., P.D., S.J.F., M.R.R.); the Universitatsklinik Magdeburg, Klinik fur Kardiologie, Magdeburg, Germany (J.C.G.); and the Institute of Molecular Cardiology, Department of Physiology and Biophysics, SUNY Stony Brook, Stony Brook, NY (H.Y., I.S.C.). Dr Yu is now at the New York College of Osteopathic Medicine, Old Westbury, NY.

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, PH7West-321, New York, NY 10032. E-mail mrr1{at}columbia.edu

Background— We tested the hypothesis that I_Ca,L is important to the development of cardiac memory.

Methods and Results— The effects of L-type Ca²⁺ channel blockade and ß-blockade were tested on acutely anesthetized and on chronically instrumented, conscious dogs. Short-term memory (STM) was induced by 2 hours of ventricular pacing and long-term memory (LTM) by ventricular pacing for 21 days. STM dogs received placebo, nifedipine, or propranolol, and LTM dogs received placebo, atenolol, or amlodipine. AT₁ receptor blockade (candesartan) and ACE inhibition (trandolapril) were also tested in LTM. Microelectrodes were used to record transmembrane potentials from isolated epicardial and endocardial slabs using a protocol simulating STM in intact animals. Left ventricular epicardial myocytes from LTM or sham control dogs were dissociated, and I_Ca,L was recorded (whole-cell patch-clamp technique). Evolution of STM and LTM was attenuated by I_Ca,L blockers but not ß-blockers. Neither AT₁ receptor blockade nor ACE inhibition suppressed LTM. In microelectrode experiments, pacing induced an epicardial-endocardial gradient change mimicking STM that was suppressed by nifedipine. In patch-clamp experiments, peak I_Ca,L density in LTM and control were equivalent, but activation was more positive and time constants of inactivation longer in LTM (P<0.05).

Conclusions— I_Ca,L blockade but not ß-adrenergic blockade suppresses cardiac memory. LTM evolution is unaffected by angiotensin II blockade and is associated with altered I_Ca,L kinetics.

Key Words: calcium • pacing • ventricles • electrocardiography • electrophysiology

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