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Titin based viscosity in ventricular physiology: An integrative investigation of PEVK-actin interactions

Item Type:Article
Title:Titin based viscosity in ventricular physiology: An integrative investigation of PEVK-actin interactions
Creators Name:Chung, C.S. and Methawasin, M. and Nelson, O.L. and Radke, M.H. and Hidalgo, C.G. and Gotthardt, M. and Granzier, H.L.
Abstract:Viscosity is proposed to modulate diastolic function, but only limited understanding of the source(s) of viscosity exists. In vitro experiments have shown that the proline-glutamic acid-valine-lysine (PEVK) rich element of titin interacts with actin, causing a viscous force in the sarcomere. It is unknown whether this mechanism contributes to viscosity in vivo. We tested the hypothesis that PEVK-actin interaction causes cardiac viscosity and is important in vivo via an integrative physiological study on a unique PEVK knockout (KO) model. Both skinned cardiomyocytes and papillary muscle fibers were isolated from wildtype (WT) and PEVK KO mice and passive viscosity was examined using stretch-hold-release and sinusoidal analysis. Viscosity was reduced by ~60% in KO myocytes and ~50% in muscle fibers at room temperature. The PEVK-actin interaction was not modulated by temperature or diastolic calcium, but was increased by lattice compression. Stretch-hold and sinusoidal frequency protocols on intact isolated mouse hearts showed a smaller, 30-40% reduction in viscosity, possibly due to actomyosin interactions, and showed that microtubules did not contribute to viscosity. Transmitral Doppler echocardiography similarly revealed a 40% decrease in LV chamber viscosity in the PEVK KO in vivo. This integrative study is the first to quantify the influence of a specific molecular (PEVK-actin) viscosity in vivo and shows that PEVK-actin interactions are an important physiological source of viscosity.
Keywords:Titin/Connectin, Actin, Diastole, In vivo, Passive Force, Animals, Mice
Source:Journal of Molecular and Cellular Cardiology
Publisher:Elsevier (The Netherlands)
Page Range:428-434
Date:September 2011
Official Publication:https://doi.org/10.1016/j.yjmcc.2011.06.006
PubMed:View item in PubMed

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