An integrated mechanism of cardiomyocyte nuclear Ca2+ signaling

Cristián Ibarra, Jose Miguel Vicencio, Manuel Varas-Godoy, Enrique Jaimovich, Beverly A Rothermel, Per Uhlén, Joseph A Hill, Sergio Lavandero

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations


In cardiomyocytes, Ca2+ plays a central role in governing both contraction and signaling events that regulate gene expression. Current evidence indicates that discrimination between these two critical functions is achieved by segregating Ca2+ within subcellular microdomains: transcription is regulated by Ca2+ release within nuclear microdomains, and excitation-contraction coupling is regulated by cytosolic Ca2+. Accordingly, a variety of agonists that control cardiomyocyte gene expression, such as endothelin-1, angiotensin-II or insulin-like growth factor-1, share the feature of triggering nuclear Ca2+ signals. However, signaling pathways coupling surface receptor activation to nuclear Ca2+ release, and the phenotypic responses to such signals, differ between agonists. According to earlier hypotheses, the selective control of nuclear Ca2+ signals by activation of plasma membrane receptors relies on the strategic localization of inositol trisphosphate receptors at the nuclear envelope. There, they mediate Ca2+ release from perinuclear Ca2+ stores upon binding of inositol trisphosphate generated in the cytosol, which diffuses into the nucleus. More recently, identification of such receptors at nuclear membranes or perinuclear sarcolemmal invaginations has uncovered novel mechanisms whereby agonists control nuclear Ca2+ release. In this review, we discuss mechanisms for the selective control of nuclear Ca2+ signals with special focus on emerging models of agonist receptor activation.

Original languageEnglish (US)
Pages (from-to)40-48
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
StatePublished - Oct 1 2014


  • Angiotensin II
  • Cardiomyocyte
  • Endothelin-1
  • Insulin-like growth factor-1
  • Nuclear Ca
  • Sarcolemmal receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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