title: Cardiac ablation of Rheb1 reduces sodium currents in infant mice.
abstract: OBJECTIVE
  The Ras homolog enriched in brain gene (Rheb) is a center player within the insulin/Rheb/Mammalian Target of Rapamycin (mTOR) pathway, and plays a critical role in regulating cellular growth. Rheb-/- embryos have been reported to die around midgestation, due to the defects of the development of the cardiovascular system. Recent studies from ours and another group consistently showed that Rheb1 was indispensable for the cardiac hypertrophic growth after early postnatal period. Besides that, we also found that Rheb1 a-MHC-Cre (cKO) mice exhibited ventricular tachycardia. However, the precise mechanism by which Rheb1 knockout causes ventricular arrhythmia in these mice is still unclear.
  
  
  METHODS
  Mouse cardiomyocytes were isolated using 10 days suckling Rheb1 cKO and wide type mice using Collagenase Type II. Sodium currents and L-type calcium currents were recorded using the whole-cell patch clamping technique.
  
  
  RESULTS
  The sodium current density of ventricular cardiomyocytes from Rheb1 cKO mice was decreased by about 60%. Significant left shift but no slope altered was observed in activation curve with V1/2 values of -35.35 ± 1.12 mV for Rheb1 cKO group and -40.72 ± 1.18 mV for the controls. In addition, the area of window current, which refers the overlap of normalized activation and inactivation, was larger in Rheb1 cKO mice. Moreover, the sodium current, in general, was recovered much slower in Rheb1 cKO mice than that of the controls. However, L-type calcium currents were preserved in Rheb1 cKO mice.
  
  
  CONCLUSIONS
  Sodium currents are decreased in Rheb1 cKO mice, which might be responsible for the phenotype of arrhythima in Rheb1 cKO mice. Understanding the molecular composition of sodium ion channel complexes in the heart of these Rheb1 cKO mice will be critical to develop innovative and effective therapies for the treatment of cardiac arrhythmia.
authors: Department of Cardiology, First Affiliated Hospital of Nanjing Medical University Nanjing 210029, China ; Linhu Ward, Maanshan Municipal People's Hospital Maanshan 243021, China.
authors: Hang
authors: H
authors: Wu
authors: Department of Cardiology, First Affiliated Hospital of Nanjing Medical University Nanjing 210029, China.
authors: Zhong-Lin
authors: ZL
authors: Han
authors: Department of Cardiology, First Affiliated Hospital of Nanjing Medical University Nanjing 210029, China ; MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University Nanjing 210061, China.
authors: Yun-Shan
authors: YS
authors: Cao
authors: Department of Cardiology, First Affiliated Hospital of Nanjing Medical University Nanjing 210029, China.
authors: Shenghui
authors: S
authors: Lin
authors: Department of Cardiology, First Affiliated Hospital of Nanjing Medical University Nanjing 210029, China.
authors: Xinli
authors: X
authors: Li
keywords: Arrhythmia; L-type calcium currents; Rheb1; patch clamp; sodium currents