Microstructure-Based Monte Carlo Simulation of Ca2+ Dynamics Evoking Cardiac Calcium Channel Inactivation

• Kawazu Toshihiro

  Division of Bioengineering, Graduate School of Engineering Science, Osaka University

• Murakami Shingo

  Division of Molecular and Cellular Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University The Center for Advanced Medical Engineering and Informatics, Osaka University

• Adachi-Akahane Satomi

  Department of Pharmacology, School of Medicine, Faculty of Medicine, Graduate School of Medical Sciences, Toho University

• Findlay Ian

  CNRS UMR 6542, Faculté des Sciences, Université François-Rabelais de Tours

• Ait-Haddou Rachid

  The Center for Advanced Medical Engineering and Informatics, Osaka University

• Kurachi Yoshihisa

  Division of Molecular and Cellular Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University The Center for Advanced Medical Engineering and Informatics, Osaka University

• Nomura Taishin

  Division of Bioengineering, Graduate School of Engineering Science, Osaka University The Center for Advanced Medical Engineering and Informatics, Osaka University

抄録

Ca²⁺ dynamics underlying cardiac excitation-contraction coupling are essential for heart functions. In this study, we constructed microstructure-based models of Ca²⁺ dynamics to simulate Ca²⁺ influx through individual L-type calcium channels (LCCs), an effective Ca²⁺ diffusion within the cytoplasmic space and in the dyadic space, and the experimentally observed calcium-dependent inactivation (CDI) of the LCCs induced by local and global Ca²⁺ sensing. The models consisted of LCCs with distal and proximal Ca²⁺ (Calmodulin-Ca²⁺ complex) binding sites. In one model, the intracellular space was organelle-free cytoplasmic space, and the other was with a dyadic space including sarcoplasmic reticulum membrane. The Ca²⁺ dynamics and CDI of the LCCs in the model with and without the dyadic space were then simulated using the Monte Carlo method. We first showed that an appropriate set of parameter values of the models with effectively extra-slow Ca²⁺ diffusion enabled the models to reproduce major features of the CDI process induced by the local and global sensing of Ca²⁺ near LCCs as measured with single and two spatially separated LCCs by Imredy and Yue (Neuron. 1992;9:197-207). The effective slow Ca²⁺ diffusion might be due to association and dissociation of Ca²⁺ and Calmodulin (CaM). We then examined how the local and global CDIs were affected by the presence of the dyadic space. The results suggested that in microstructure modeling of Ca²⁺ dynamics in cardiac myocytes, the effective Ca²⁺ diffusion under CaM-Ca²⁺ interaction, the nanodomain structure of LCCs for detailed CDI, and the geometry of subcellular space for modeling dyadic space should be considered.<br>

収録刊行物

• The Journal of Physiological Sciences

  The Journal of Physiological Sciences 58 (7), 471-480, 2008

  一般社団法人　日本生理学会

キーワード

• calcium
• L-type calcium channel
• dyadic space
• Monte Carlo simulation

詳細情報

• CRID: 1390282680230703232
• NII論文ID: 10027710920
• NII論文ID: 130004466949
• NII書誌ID: AA12129145
• DOI: 10.2170/physiolsci.rp013208
• ISSN: 18806562
• ISSN: 18806546
• NDL書誌ID: 9752858
• PubMed: 18928642
• Web Site: http://id.ndl.go.jp/bib/9752858
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I9752858
• Web Site: https://search.jamas.or.jp/link/ui/2009144997
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可