a 50% reduction of excitability but not of intercellular coupling affects conduction velocity restitution and activation delay in the mouse heart减少了50%的兴奋性而不是胞间耦合的影响传导速度恢复和激活延迟鼠标的心.pdfVIP

A 50% Reduction of Excitability but Not of Intercellular Coupling Affects Conduction Velocity Restitution and Activation Delay in the Mouse Heart ` 1,2 1 2 1,3,4 Mera Stein , Toon A. B. van Veen , Richard N. W. Hauer , Jacques M. T. de Bakker , Harold V. M. van Rijen1* 1 Division of Heart Lungs, Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands, 2 Division of Heart Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands, 3 Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands, 4 Heart Failure Research Center, Academic Medical Center, Amsterdam, The Netherlands Abstract Introduction: Computer simulations suggest that intercellular coupling is more robust than membrane excitability with regard to changes in and safety of conduction. Clinical studies indicate that SCN5A (excitability) and/or Connexin43 (Cx43, intercellular coupling) expression in heart disease is reduced by approximately 50%. In this retrospective study we assessed the effect of reduced membrane excitability or intercellular coupling on conduction in mouse models of reduced excitability or intercellular coupling. Methods and Results: Epicardial activation mapping of LV and RV was performed on Langendorff-perfused mouse hearts having the following: 1) Reduced excitability: Scn5a haploinsufficient mice; and 2) reduced intercellular coupling: Cx43CreER(T)/fl mice, uninduced (50% Cx43) or induced (10% Cx43) with Tamoxifen. Wild type (WT) littermates were used as control. Conduction velocity (CV) restitution and activation delay were determined longitudinal and transversal to fiber direction during S S pacing and S S