title: Cardiac memory evolves with age in association with development of the transient outward current.
abstract: BACKGROUND
  Calcium-insensitive transient outward current (I(to)) is important to the development of cardiac memory (CM), which itself reflects the capacity of the heart to remodel electrophysiologically. We used cardiac pacing to test the hypothesis that CM evolution can be explained by developmental maturation of I(to).
  
  
  RESULTS
  Acutely anesthetized dogs from 1 day old to adult were paced from the left ventricle (VP, n=29) or left atrial appendage (AP, n=12) to induce CM. T-wave vector displacement (TVD) obtained during VP was greater than with AP (adults, 0.39+/-0.06 mV; neonates, 0.04+/-0.01 mV; P<0.05). TVD began to increase at approximately 40 days of age, reaching adult levels by approximately 200 days. Microelectrode studies performed in 18 dogs (ages 3 to 94 days) after completing the CM protocol and 20 additional dogs (1 day old to adult) revealed that the epicardial action potential notch was absent in neonates, became apparent in the young, and was deepest in adults. The relationship between TVD and epicardial notch was such that as notch magnitude increased, TVD increased (r=-0.65, P<0.05). KChIP2 and Kv4.3 mRNA (measured via reverse transcription-polymerase chain reaction) also increased with age.
  
  
  CONCLUSIONS
  The inducibility of CM gradually increases with age in association with evolution of the epicardial action potential notch and mRNA expression for KChIP2 and Kv4.3. This suggests that the capacity of the heart to remodel electrophysiologically and to manifest memory during development depends in part on evolution of the determinants of I(to).
authors.affiliation: Center for Molecular Therapeutics, Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
authors.forename: Alexei N
authors.initials: AN
authors.lastname: Plotnikov
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Sosunov
authors.forename: Kornelis W
authors.initials: KW
authors.lastname: Patberg
authors.forename: Evgeny P
authors.initials: EP
authors.lastname: Anyukhovsky
authors.forename: Ravil Z
authors.initials: RZ
authors.lastname: Gainullin
authors.forename: Iryna N
authors.initials: IN
authors.lastname: Shlapakova
authors.forename: Ganga
authors.initials: G
authors.lastname: Krishnamurthy
authors.forename: Peter
authors.initials: P
authors.lastname: Danilo
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rosen
mesh_terms: D000200:Action Potentials; D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006329:Heart Conduction System / Q000254:growth & development* / Q000502:physiology; D017136:Ion Transport; D051605:Kv Channel-Interacting Proteins; D008297:Male; D024642:Potassium Channels, Voltage-Gated / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051672:Shal Potassium Channels
chemical_list: D002135:Calcium-Binding Proteins; D051605:Kv Channel-Interacting Proteins; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051672:Shal Potassium Channels; D002118:Calcium