title: Ventricular hypertrophy amplifies transmural dispersion of repolarization by preferentially increasing the late sodium current in endocardium.
abstract: BACKGROUND
  The late sodium current (INa-L) contributes importantly to rate-dependent change in action potential duration (APD) and transmural dispersion of repolarization (TDR). However, little is known about the mechanisms of increased APD rate-dependence and amplified TDR in left ventricular hypertrophy (LVH) and failure. The purpose of this study was to investigate the role of INa-L in rate-adaptation of transmural APD heterogeneity.
  
  
  METHODS
  APD, its rate-dependence and INa-L current were examined in myocytes isolated from the endocardium and epicardium of the control and LVH rabbits. AP was recorded using the standard microelectrode technique, and INa-L was recorded using the whole-cell patch clamp technique.
  
  
  RESULTS
  Early afterdepolarizations (EADs) were frequently recorded in the isolated myocytes of the LVH rabbits but not in those of controls. LVH prolonged APD more significantly in the endocardial myocytes than in the epicardium (31.7±3.4 vs. 21.6±1.5% n=6, p<0.05), leading to a marked increase in TDR. LVH endocardial myocytes exhibited a greater rate-dependent change in APD compared to the epicardial myocytes. INa-L densities were significantly increased in both LVH endocardium and epicardium. However, LVH increased the INa-L density preferentially in the endocardial myocytes compared to the epicardial myocytes (54.5±4.8% vs. 39.2±3.3%, n=6, p<0.05).
  
  
  CONCLUSIONS
  Our results demonstrate that LVH increased the INa-L preferentially in the endocardium over the epicardium, which contributes importantly to the stronger rate-dependent change in repolarization and longer APD in the endocardium. This results in an amplified TDR capable of initiating EAD and ventricular arrhythmias.
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, PA; College of Life Science, South-Central University for Nationalities, Wuhan, China. Electronic address: dlguo2013@gmail.com.
authors.forename: Donglin
authors.initials: D
authors.lastname: Guo
authors.affiliation: College of Life Science, South-Central University for Nationalities, Wuhan, China.
authors.forename: Mengfei
authors.initials: M
authors.lastname: Yu
authors.affiliation: College of Life Science, South-Central University for Nationalities, Wuhan, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, PA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Cox
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, PA.
authors.forename: Tengxian
authors.initials: T
authors.lastname: Liu
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, PA; Jefferson Medical College, Philadelphia, PA.
authors.forename: Gan-Xin
authors.initials: GX
authors.lastname: Yan
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D004699:Endocardium / Q000166:cytology* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D032342:Muscle Cells / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D015222:Sodium Channels
keywords: Action potential duration; Late sodium current; Left ventricular hypertrophy; Rate dependence; Transmural dispersion of repolarization