Inositol 1,4,5-Trisphosphate Directs Ca2+ Flow between Mitochondria and the Endoplasmic/Sarcoplasmic Reticulum: A Role in Regulating Cardiac Autonomic Ca2+ Spiking
AUTOR(ES)
Jaconi, Marisa
FONTE
The American Society for Cell Biology
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=14888Documentos Relacionados
- Diffusion of inositol 1,4,5-trisphosphate but not Ca2+ is necessary for a class of inositol 1,4,5-trisphosphate-induced Ca2+ waves.
- Agonist-induced Ca2+ entry determined by inositol 1,4,5-trisphosphate recognition
- RACK1 binds to inositol 1,4,5-trisphosphate receptors and mediates Ca2+ release
- Activating calcium release through inositol 1,4,5-trisphosphate receptors without inositol 1,4,5-trisphosphate
- Bcl-XL affects Ca2+ homeostasis by altering expression of inositol 1,4,5-trisphosphate receptors