Journal article
Titin based viscosity in ventricular physiology: An integrative investigation of PEVK–actin interactions
Journal of molecular and cellular cardiology, Vol.51(3), pp.428-434
2011
Handle:
https://hdl.handle.net/2376/102877
PMCID: PMC3150406
PMID: 21708170
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.
► Our goal was to study the role of titin-based viscosity in diastolic function. ► The titin PEVK element interacts in vitro with actin to create viscosity; we used a mouse deficient in PEVK. ► PEVK KO reduces viscosity >
50% in skinned tissue in vitro and >
30% in hearts in vivo. ► The PEVK–actin interaction is an important physiologic source of viscosity.
Metrics
9 Record Views
Details
- Title
- Titin based viscosity in ventricular physiology: An integrative investigation of PEVK–actin interactions
- Creators
- Charles S Chung - Molecular Cardiovascular Research Program, Sarver Heart Center, Department of Physiology, University of Arizona, Tucson AZ, USAMethajit Methawasin - Molecular Cardiovascular Research Program, Sarver Heart Center, Department of Physiology, University of Arizona, Tucson AZ, USAO. Lynne Nelson - Department of Veterinary Clinical Medicine, Washington State University, Pullman WA, USAMichael H Radke - Max-Delbrück-Center for Molecular Medicine (MDC), Berlin-Buch, GermanyCarlos G Hidalgo - Molecular Cardiovascular Research Program, Sarver Heart Center, Department of Physiology, University of Arizona, Tucson AZ, USAMichael Gotthardt - Max-Delbrück-Center for Molecular Medicine (MDC), Berlin-Buch, GermanyHenk L Granzier - Molecular Cardiovascular Research Program, Sarver Heart Center, Department of Physiology, University of Arizona, Tucson AZ, USA
- Publication Details
- Journal of molecular and cellular cardiology, Vol.51(3), pp.428-434
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- Elsevier Ltd
- Identifiers
- 99900546505801842
- Language
- English
- Resource Type
- Journal article