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

Jaconi, Marisa; Bony, C.; Richards, S. M.; Terzic, A.; Arnaudeau, Serge; Vassort, G.; Puceat, M.

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Title		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
Authors		Jaconi, Marisa Bony, C. Richards, S. M. Terzic, A. Arnaudeau, Serge Vassort, G. Puceat, M.
Published in		Molecular biology of the cell. 2000, vol. 11, no. 5, p. 1845-1858
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
Identifiers		PMID: 10793156
Full text		Article - Limited access to UNIGE Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC14888/pdf/mk001845.pdf
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
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. https://archive-ouverte.unige.ch/unige:11359