Role of L-type calcium channels in pacing-induced short-term and long-term cardiac memory in canine heart.
BACKGROUND
We tested the hypothesis that ICa,L is important to the development of cardiac memory.


RESULTS
The effects of L-type Ca2+ channel blockade and beta-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 ICa,L was recorded (whole-cell patch-clamp technique). Evolution of STM and LTM was attenuated by ICa,L blockers but not beta-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 ICa,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
ICa,L blockade but not beta-adrenergic blockade suppresses cardiac memory. LTM evolution is unaffected by angiotensin II blockade and is associated with altered ICa,L kinetics.
Plotnikov
Alexei N
AN
Center for Molecular Therapeutics, Department of Pharmacology, College of Physicians and Surgeons of Columbia University, 630 W 168 St, PH7West-321, New York, NY 10032, USA.
Yu
Hangang
H
Geller
J Christoph
JC
Gainullin
Ravil Z
RZ
Chandra
Parag
P
Patberg
Kornelis W
KW
Friezema
Steven
S
Danilo
Peter
P
Cohen
Ira S
IS
Feinmark
Steven J
SJ
Rosen
Michael R
MR
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D002304:Cardiac Pacing, Artificial; D002478:Cells, Cultured; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011433:Propranolol / Q000494:pharmacology; D016276:Ventricular Function
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D011433:Propranolol; D009543:Nifedipine; D002118:Calcium