Inositol 1,4,5-trisphosphate directs Ca2+ flow between mitochondria and the endoplasmic/sarcoplasmic reticulum: A role in regulating cardiac autonomic Ca2+ spiking

Marisa Jaconi, Claire Bony, Stephen M. Richards, André Terzic, Serge Arnaudeau, Guy Vassort, Michel Pucéat

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

The signaling role of the Ca2+ releaser inositol 1,4,5-trisphosphate (IP3) has been associated with diverse cell functions. Yet, the physiological significance of IP3 in tissues that feature a ryanodine- sensitive sarcoplasmic reticulum has remained elusive. IP3 generated by photolysis of caged IP3 or by purinergic activation of phospholipase Cγ slowed down or abolished autonomic Ca2+ spiking in neonatal rat cardiomyocytes. Microinjection of heparin, blocking dominant-negative fusion protein, or anti-phospholipase Cγ antibody prevented the IP3-mediated purinergic effect. IP3 triggered a ryanodine- and caffeine-insensitive Ca2+ release restricted to the perinuclear region. In cells loaded with Rhod2 or expressing a mitochondria-targeted cameleon and TMRM to monitor mitochondrial Ca2+ and potential, IP3 induced transient Ca2+ loading and depolarization of the organelles. These mitochondrial changes were associated with Ca2+ depletion of the sarcoplasmic reticulum and preceded the arrest of cellular Ca2+ spiking. Thus, IP3 acting within a restricted cellular region regulates the dynamic of calcium flow between mitochondria and the endoplasmic/sarcoplasmic reticulum. We have thus uncovered a novel role for IP3 in excitable cells, the regulation of cardiac autonomic activity.

Original languageEnglish (US)
Pages (from-to)1845-1858
Number of pages14
JournalMolecular biology of the cell
Volume11
Issue number5
DOIs
StatePublished - May 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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