I(Kr) contributes to the altered ventricular repolarization that determines long-term cardiac memory.
OBJECTIVE
Cardiac memory (CM) is characterized by an altered T-wave morphology, which reflects altered repolarization gradients. We hypothesized that the delayed rectifier currents, I(Kr) and I(Ks), might contribute to these repolarization changes.


METHODS
We studied conscious, chronically instrumented dogs paced from the postero-lateral left ventricular (LV) wall at rates 5-10% faster than sinus rate for 3 weeks. ECGs during sinus rhythm were recorded on days 0, 7, 14 and 21 of pacing. Within 3 weeks, CM achieved steady state, hearts were excised, and epicardial and endocardial tissues and myocytes were studied.


RESULTS
In unpaced controls, action potential duration to 50% and 90% repolarization (APD) in epicardium was shorter than in endocardium (P < 0.05); in CM epicardial APD increased at CL > or = 500 ms, while endocardial APD was either unchanged or decreased such that the transmural gradient seen in controls diminished (P < 0.05). A transmural I(Kr) gradient occurred in controls (epicardium>endocardium, P < 0.05) and was reversed in CM. No I(Ks) transmural gradient was found in controls, while in CM endocardial I(Ks) was greater than epicardial at greater than +50 mV. Canine ERG (cERG) mRNA and protein in epicardium > endocardium in controls (P < 0.05), and this difference was lost in CM. Expression levels of KCNQ1 and KCNE1 protein were similar in all groups.


CONCLUSIONS
A transcriptionally induced change in epicardial I(Kr) contributes to the altered ventricular repolarization that characterizes CM.
Obreztchikova
Maria N
MN
Center for Molecular Therapeutics, Department of Pharmacology and Pediatrics, College of Physicians and Surgeons of Columbia University, 630 West 168 Street, PH 7West-321, New York, NY 10032, USA.
Patberg
Kornelis W
KW
Plotnikov
Alexei N
AN
Ozgen
Nazira
N
Shlapakova
Irina N
IN
Rybin
Andrew V
AV
Sosunov
Eugene A
EA
Danilo
Peter
P
Anyukhovsky
Evgeny P
EP
Robinson
Richard B
RB
Rosen
Michael R
MR
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004562:Electrocardiography; D004699:Endocardium / Q000378:metabolism / Q000502:physiology; D051638:Ether-A-Go-Go Potassium Channels / Q000032:analysis / Q000235:genetics; D006352:Heart Ventricles; D051657:KCNQ1 Potassium Channel / Q000032:analysis / Q000235:genetics; D008564:Membrane Potentials / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010496:Pericardium / Q000378:metabolism / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D020257:Ventricular Remodeling
D051638:Ether-A-Go-Go Potassium Channels; C489622:KCNE1 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated