How Does the Ca<sup>2+</sup>-paradox Injury Induce Contracture in the Heart?—A Combined Study of the Intracellular Ca<sup>2+</sup> Dynamics and Cell Structures in Perfused Rat Hearts—

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Author(s)

    • Mani Hiroki
    • Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Graduate School of Medical Science|Department of Molecular Genetics and Laboratory Medicine, Kyoto Prefectural University of Medicine, Graduate School of Medical Science
    • Tanaka Hideo
    • Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Graduate School of Medical Science
    • Adachi Tetsuya
    • Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Graduate School of Medical Science
    • Ikegawa Masaya
    • Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Graduate School of Medical Science
    • Dai Ping
    • Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Graduate School of Medical Science
    • Fujita Naohisa
    • Department of Molecular Genetics and Laboratory Medicine, Kyoto Prefectural University of Medicine, Graduate School of Medical Science
    • Takamatsu Tetsuro
    • Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Graduate School of Medical Science

Abstract

The calcium (Ca<sup>2+</sup>)-paradox injury of the heart, induced by restoration of extracellular Ca<sup>2+</sup> after its short-term depletion, is known to provoke cardiomyocyte contracture. However, undetermined is how the Ca<sup>2+</sup>-paradox provokes such a distinctive presentation of myocytes in the heart. To address this, we imaged sequential intracellular Ca<sup>2+</sup> dynamics and concomitant structures of the subepicardial ventricular myocytes in fluo3-loaded, Langendorff-perfused rat hearts produced by the Ca<sup>2+</sup> paradox. Under rapid-scanning confocal microscopy, repletion of Ca<sup>2+</sup> following its depletion produced high-frequency Ca<sup>2+</sup> waves in individual myocytes with asynchronous localized contractions, resulting in contracture within 10 min. Such alterations of myocytes were attenuated by 5-mM NiCl<sub>2</sub>, but not by verapamil, SEA0400, or combination of ryanodine and thapsigargin, indicating a contribution of non-specific transmembrane Ca<sup>2+</sup> influx in the injury. However, saponin-induced membrane permeabilization of Ca<sup>2+</sup> showed no apparent contracture despite the emergence of high-frequency Ca<sup>2+</sup> waves, indicating an essential role of myocyte-myocyte and myocyte-extracellular matrix (ECM) mechanical connections in the Ca<sup>2+</sup> paradox. In immunohistochemistry Ca<sup>2+</sup> depletion produced separation of the intercalated disc that expresses cadherin and dissipation of <font face="roman">β</font>-dystroglycan located along the sarcolemma. Taken together, along with the trans-sarcolemmal Ca<sup>2+</sup> influx, disruption of cell-cell and cell-ECM connections is essential for contracture in the Ca<sup>2+</sup>-paradox injury.

Journal

  • ACTA HISTOCHEMICA ET CYTOCHEMICA

    ACTA HISTOCHEMICA ET CYTOCHEMICA 48(1), 1-8, 2015

    JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY

Codes

  • NII Article ID (NAID)
    130004902931
  • Text Lang
    ENG
  • ISSN
    0044-5991
  • Data Source
    J-STAGE 
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