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

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)195-200
Number of pages6
JournalJournal of Physiological Sciences
Issue number2
StatePublished - Mar 19 2015
Externally publishedYes


  • Adenlyl cyclase
  • Calcium
  • Computational analysis
  • Cyclic AMP
  • Oscillation
  • Subtype

ASJC Scopus subject areas

  • Physiology


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