

Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC14888/pdf/mk001845.pdf
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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 |
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Authors | ||
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 | |
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![]() ![]() Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC14888/pdf/mk001845.pdf |
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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 |