How Does the Ca²⁺-paradox Injury Induce Contracture in the Heart?—A Combined Study of the Intracellular Ca²⁺ Dynamics and Cell Structures in Perfused Rat Hearts—

• 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

抄録

The calcium (Ca²⁺)-paradox injury of the heart, induced by restoration of extracellular Ca²⁺ after its short-term depletion, is known to provoke cardiomyocyte contracture. However, undetermined is how the Ca²⁺-paradox provokes such a distinctive presentation of myocytes in the heart. To address this, we imaged sequential intracellular Ca²⁺ dynamics and concomitant structures of the subepicardial ventricular myocytes in fluo3-loaded, Langendorff-perfused rat hearts produced by the Ca²⁺ paradox. Under rapid-scanning confocal microscopy, repletion of Ca²⁺ following its depletion produced high-frequency Ca²⁺ waves in individual myocytes with asynchronous localized contractions, resulting in contracture within 10 min. Such alterations of myocytes were attenuated by 5-mM NiCl₂, but not by verapamil, SEA0400, or combination of ryanodine and thapsigargin, indicating a contribution of non-specific transmembrane Ca²⁺ influx in the injury. However, saponin-induced membrane permeabilization of Ca²⁺ showed no apparent contracture despite the emergence of high-frequency Ca²⁺ waves, indicating an essential role of myocyte-myocyte and myocyte-extracellular matrix (ECM) mechanical connections in the Ca²⁺ paradox. In immunohistochemistry Ca²⁺ depletion produced separation of the intercalated disc that expresses cadherin and dissipation of β-dystroglycan located along the sarcolemma. Taken together, along with the trans-sarcolemmal Ca²⁺ influx, disruption of cell-cell and cell-ECM connections is essential for contracture in the Ca²⁺-paradox injury.

収録刊行物

• Ａｃｔａ　Ｈｉｓｔｏｃｈｅｍｉｃａ　ｅｔ　Ｃｙｔｏｃｈｅｍｉｃａ

  Ａｃｔａ　Ｈｉｓｔｏｃｈｅｍｉｃａ　ｅｔ　Ｃｙｔｏｃｈｅｍｉｃａ 48 (1), 1-8, 2015

  日本組織細胞化学会

キーワード

• Ca²⁺ paradox
• heart
• Ca²⁺ wave
• contracture
• β-dystroglycan

詳細情報

• CRID: 1390282679837587968
• NII論文ID: 130004902931
• DOI: 10.1267/ahc.14059
• ISSN: 13475800
• ISSN: 00445991
• Web Site: https://www.jstage.jst.go.jp/article/ahc/48/1/48_14059/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016061326
• 本文言語コード: en
• データソース種別:
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  • Crossref
  • CiNii Articles
  • KAKEN
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