The Journal of Physiological Sciences

, Volume 65, Issue 2, pp 195–200

Oscillation of cAMP and Ca2+ in cardiac myocytes: a systems biology approach

  • Takehisa Kamide
  • Satoshi Okumura
  • Samik Ghosh
  • Yoko Shinoda
  • Yasumasa Mototani
  • Yoshiki Ohnuki
  • Huiling Jin
  • Wenqian Cai
  • Kenji Suita
  • Itaru Sato
  • Masanari Umemura
  • Takayuki Fujita
  • Utako Yokoyama
  • Motohiko Sato
  • Kazuharu Furutani
  • Hiroaki Kitano
  • Yoshihiro Ishikawa
Short Communication

Abstract

Cyclic adenosine monophosphate (cAMP) and Ca2+ levels may oscillate in harmony within excitable cells; a mathematical oscillation loop model, the Cooper model, of these oscillations was developed two decades ago. However, in that model all adenylyl cyclase (AC) isoforms were assumed to be inhibited by Ca2+, and it is now known that the heart expresses multiple AC isoforms, among which the type 5/6 isoforms are Ca2+-inhibitable whereas the other five (AC2, 3, 4, 7, and 9) are not. We used a computational systems biology approach with CellDesigner simulation software to develop a comprehensive graphical map and oscillation loop model for cAMP and Ca2+. This model indicated that Ca2+-mediated inhibition of AC is essential to create oscillations of Ca2+ and cAMP, and the oscillations were not altered by incorporation of phosphodiesterase-mediated cAMP hydrolysis or PKA-mediated inhibition of AC into the model. More importantly, they were created but faded out immediately in the co-presence of Ca2+-noninhibitable AC isoforms. Because the subcellular locations of AC isoforms are different, spontaneous cAMP and Ca2+ oscillations may occur within microdomains containing only Ca2+-inhibitable isoforms in cardiac myocytes, which might be necessary for fine tuning of excitation–contraction coupling.

Keywords

Adenlyl cyclase Subtype Computational analysis Oscillation Cyclic AMP Calcium 

Supplementary material

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Supplementary material 1 (DOCX 23 kb)
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Supplementary material 2 (PDF 9 kb)
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Supplementary material 3 (PDF 8 kb)
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Supplementary material 4 (PDF 947 kb)
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Supplementary material 5 (PDF 401 kb)
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Supplementary material 6 (PDF 10 kb)

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Copyright information

© The Physiological Society of Japan and Springer Japan 2015

Authors and Affiliations

  • Takehisa Kamide
    • 1
  • Satoshi Okumura
    • 1
    • 2
  • Samik Ghosh
    • 3
  • Yoko Shinoda
    • 2
  • Yasumasa Mototani
    • 2
  • Yoshiki Ohnuki
    • 2
  • Huiling Jin
    • 1
  • Wenqian Cai
    • 1
  • Kenji Suita
    • 1
  • Itaru Sato
    • 1
  • Masanari Umemura
    • 1
  • Takayuki Fujita
    • 1
  • Utako Yokoyama
    • 1
  • Motohiko Sato
    • 1
    • 4
  • Kazuharu Furutani
    • 5
    • 6
  • Hiroaki Kitano
    • 3
    • 7
    • 8
  • Yoshihiro Ishikawa
    • 1
  1. 1.Cardiovascular Research InstituteYokohama City University Graduate School of MedicineYokohamaJapan
  2. 2.Department of PhysiologyTsurumi University School of Dental MedicineYokohamaJapan
  3. 3.The Systems Biology InstituteTokyoJapan
  4. 4.Department of PhysiologyAichi Medical UniversityNagakuteJapan
  5. 5.Department of Pharmacology, Graduate School of MedicineOsaka UniversityOsakaJapan
  6. 6.Center for Advanced Medical Engineering and InformaticsOsaka UniversityOsakaJapan
  7. 7.Okinawa Institute of Science and Technology Graduate SchoolOkinawaJapan
  8. 8.Laboratory for Disease Systems ModelingRiken Center for Integrative Medical SciencesYokohamaJapan

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