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Scientific article
English

Inositol 1,4,5-trisphosphate directs Ca(2+) flow between mitochondria and the Endoplasmic/Sarcoplasmic reticulum: a role in regulating cardiac autonomic Ca(2+) spiking

Published inMolecular biology of the cell, vol. 11, no. 5, p. 1845-1858
Publication date2000
Abstract

The signaling role of the Ca(2+) releaser inositol 1,4, 5-trisphosphate (IP(3)) has been associated with diverse cell functions. Yet, the physiological significance of IP(3) in tissues that feature a ryanodine-sensitive sarcoplasmic reticulum has remained elusive. IP(3) generated by photolysis of caged IP(3) or by purinergic activation of phospholipase Cgamma slowed down or abolished autonomic Ca(2+) spiking in neonatal rat cardiomyocytes. Microinjection of heparin, blocking dominant-negative fusion protein, or anti-phospholipase Cgamma antibody prevented the IP(3)-mediated purinergic effect. IP(3) triggered a ryanodine- and caffeine-insensitive Ca(2+) release restricted to the perinuclear region. In cells loaded with Rhod2 or expressing a mitochondria-targeted cameleon and TMRM to monitor mitochondrial Ca(2+) and potential, IP(3) induced transient Ca(2+) loading and depolarization of the organelles. These mitochondrial changes were associated with Ca(2+) depletion of the sarcoplasmic reticulum and preceded the arrest of cellular Ca(2+) spiking. Thus, IP(3) 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 IP(3) in excitable cells, the regulation of cardiac autonomic activity.

Keywords
  • Adenosine Triphosphate/metabolism/pharmacology
  • Amino Acid Sequence
  • Animals
  • Antibodies/pharmacology
  • Caffeine/metabolism/pharmacology
  • Calcium/ metabolism
  • Calcium Channels/genetics/metabolism
  • Calcium Signaling
  • Cells, Cultured
  • Endoplasmic Reticulum/ metabolism
  • Fluorescent Dyes
  • Heart/drug effects
  • Heparin/pharmacology
  • Inositol 1,4,5-Trisphosphate/ metabolism
  • Inositol 1,4,5-Trisphosphate Receptors
  • Isoenzymes/immunology/metabolism
  • Mitochondria/ metabolism
  • Molecular Sequence Data
  • Myocardium/cytology/ metabolism
  • Phospholipase C gamma
  • Rats
  • Receptors, Cytoplasmic and Nuclear/genetics/metabolism
  • Recombinant Fusion Proteins/genetics/metabolism
  • Ryanodine/metabolism/pharmacology
  • Sarcoplasmic Reticulum/ metabolism
  • Type C Phospholipases/immunology/metabolism
Citation (ISO format)
JACONI, Marisa et al. Inositol 1,4,5-trisphosphate directs Ca(2+) flow between mitochondria and the Endoplasmic/Sarcoplasmic reticulum: a role in regulating cardiac autonomic Ca(2+) spiking. In: Molecular biology of the cell, 2000, vol. 11, n° 5, p. 1845–1858.
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ISSN of the journal1059-1524
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