The role of extracellular matrix in modulation of myocyte Ca2+ signalling and contraction in the isolated rat heart
type: CreativeWork
description: Traditionally the extracellular matrix (ECM) in the heart has been thought to provide mechanical scaffolding for the contracting myocytes. However, it was observed that the amplitude of the intracellular Ca2+ transients that underlie contraction was reduced in isolated myocytes in comparison to Ca2+ transients from multicellular trabeculae. The role of ECM in myocyte Ca2+ modulation is poorly understood. We therefore hypothesised that Ca2+ handling might be modulated by (bidirectional) signalling between myocytes and the ECM, and that this important link could be lost during the standard cell isolation by enzymatic process. The aim of this thesis was to investigate the contribution of ECM in myocyte Ca2+ handling in cardiac trabeculae. To achieve this, measurements of isometric force and intracellular Ca2+ (340/380 ratio) in electrically stimulated rat cardiac trabeculae before and after enzyme exposure that dismantle the linkages between the ECM and the myocytes was continuously measured at room temperature. Immuno-histochemical techniques were used to determine the extent of loss of key proteins linking the ECM and the myocytes during this dismantling. Experiments revealed that partial enzymatic digestion increased the resting Ca2+ and stress in trabeculae. Furthermore, this study showed that there is decreased RECA-1 labelling in partial digested trabeculae and its complete absence in single myocytes but without any loss in laminin, Cxn-43, and vinculin labelling. In addition, the evaluation of ET-1 effect show neither increase in stress nor in [Ca2+]i in partial dismantled trabeculae. Additionally, the ET-1 application in isolated single myocytes significantly increase the amplitude of [Ca2+]i. Together, these results suggest the contribution of ECM components especially endothelial cells to myocyte Ca2+ modulation. Next, this study also looked at the evidence of presence of primary cilia in adult rat hearts and found no evidence of primary cilia in either ventr…
abstract: Traditionally the extracellular matrix (ECM) in the heart has been thought to provide mechanical scaffolding for the contracting myocytes. However, it was observed that the amplitude of the intracellular Ca2+ transients that underlie contraction was reduced in isolated myocytes in comparison to Ca2+ transients from multicellular trabeculae. The role of ECM in myocyte Ca2+ modulation is poorly understood. We therefore hypothesised that Ca2+ handling might be modulated by (bidirectional) signalling between myocytes and the ECM, and that this important link could be lost during the standard cell isolation by enzymatic process. The aim of this thesis was to investigate the contribution of ECM in myocyte Ca2+ handling in cardiac trabeculae. To achieve this, measurements of isometric force and intracellular Ca2+ (340/380 ratio) in electrically stimulated rat cardiac trabeculae before and after enzyme exposure that dismantle the linkages between the ECM and the myocytes was continuously measured at room temperature. Immuno-histochemical techniques were used to determine the extent of loss of key proteins linking the ECM and the myocytes during this dismantling. Experiments revealed that partial enzymatic digestion increased the resting Ca2+ and stress in trabeculae. Furthermore, this study showed that there is decreased RECA-1 labelling in partial digested trabeculae and its complete absence in single myocytes but without any loss in laminin, Cxn-43, and vinculin labelling. In addition, the evaluation of ET-1 effect show neither increase in stress nor in [Ca2+]i in partial dismantled trabeculae. Additionally, the ET-1 application in isolated single myocytes significantly increase the amplitude of [Ca2+]i. Together, these results suggest the contribution of ECM components especially endothelial cells to myocyte Ca2+ modulation. Next, this study also looked at the evidence of presence of primary cilia in adult rat hearts and found no evidence of primary cilia in either ventr…
author: Kaur, Sarbjot
license: https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm
date published: 2015
date modified: 2026-07-24T01:06:29Z
provider: University of Auckland
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: ResearchSpace@Auckland

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property ID: Handle
value: https://hdl.handle.net/2292/29006