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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

Bony, C.
Richards, S. M.
Terzic, A.
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/pharmacologyAmino Acid SequenceAnimalsAntibodies/pharmacologyCaffeine/metabolism/pharmacologyCalcium/ metabolismCalcium Channels/genetics/metabolismCalcium SignalingCells, CulturedEndoplasmic Reticulum/ metabolismFluorescent DyesHeart/drug effectsHeparin/pharmacologyInositol 1,4,5-Trisphosphate/ metabolismInositol 1,4,5-Trisphosphate ReceptorsIsoenzymes/immunology/metabolismMitochondria/ metabolismMolecular Sequence DataMyocardium/cytology/ metabolismPhospholipase C gammaRatsReceptors, Cytoplasmic and Nuclear/genetics/metabolismRecombinant Fusion Proteins/genetics/metabolismRyanodine/metabolism/pharmacologySarcoplasmic Reticulum/ metabolismType C Phospholipases/immunology/metabolism
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PMID: 10793156
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