Modeling calcium regulation of contraction, energetics, signaling, and transcription in the cardiac myocyte

Raimond L. Winslow, Mark A. Walker, Joseph L. Greenstein

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations


Calcium (Ca2+) plays many important regulatory roles in cardiac muscle cells. In the initial phase of the action potential, influx of Ca2+ through sarcolemmal voltage-gated L-type Ca2+ channels (LCCs) acts as a feed-forward signal that triggers a large release of Ca2+ from the junctional sarcoplasmic reticulum (SR). This Ca2+ drives heart muscle contraction and pumping of blood in a process known as excitation-contraction coupling (ECC). Triggered and released Ca2+ also feed back to inactivate LCCs, attenuating the triggered Ca2+ signal once release has been achieved. The process of ECC consumes large amounts of ATP. It is now clear that in a process known as excitation-energetics coupling, Ca2+ signals exert beat-to-beat regulation of mitochondrial ATP production that closely couples energy production with demand. This occurs through transport of Ca2+ into mitochondria, where it regulates enzymes of the tricarboxylic acid cycle. In excitation-signaling coupling, Ca2+ activates a number of signaling pathways in a feed-forward manner. Through effects on their target proteins, these interconnected pathways regulate Ca2+ signals in complex ways to control electrical excitability and contractility of heart muscle. In a process known as excitation-transcription coupling, Ca2+ acting primarily through signal transduction pathways also regulates the process of gene transcription. Because of these diverse and complex roles, experimentally based mechanistic computational models are proving to be very useful for understanding Ca2+ signaling in the cardiac myocyte. WIREs Syst Biol Med 2016, 8:37-67. doi: 10.1002/wsbm.1322 For further resources related to this article, please visit the WIREs website.

Original languageEnglish (US)
Pages (from-to)37-67
Number of pages31
JournalWiley Interdisciplinary Reviews: Systems Biology and Medicine
Issue number1
StatePublished - Jan 1 2016

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)


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