Sodium-calcium exchanger and R-type Ca2+ channels mediate spontaneous [Ca2+]i oscillations in magnocellular neurones of the rat supraoptic nucleus
Résumé
Isolated supraoptic neurones generate spontaneous [Ca2+]i oscillations in isolated conditions. Here we report in depth analysis of the contribution of plasmalemmal ion channels (Ca2+, Na+), Na+/Ca2+ exchanger (NCX), intracellular Ca2+ release channels (InsP3Rs and RyRs), Ca2+ storage organelles, plasma membrane Ca2+ pump and intracellular signal transduction cascades into spontaneous Ca2+ activity. While removal of extracellular Ca2+ or incubation with non-specific voltage-gated Ca2+ channel (VGCC) blocker Cd2+ suppressed the oscillations, neither Ni2+ nor TTA-P2, the T-type VGCC blockers, had an effect. Inhibitors of VGCC nicardipine, ω-conotoxin GVIA, ω-conotoxin MVIIC, ω-agatoxin IVA (for L-, N-, P and P/Q-type channels, respectively) did not affect [Ca2+]i oscillations. In contrast, a specific R-type VGCC blocker SNX-482 attenuated [Ca2+]i oscillations. Incubation with TTX had no effect, whereas removal of the extracellular Na+ or application of an inhibitor of the reverse operation mode of Na+/Ca2+ exchanger KB-R7943 blocked the oscillations. The mitochondrial uncoupler CCCP irreversibly blocked spontaneous [Ca2+]i activity. Exposure of neurones to Ca2+ mobilisers (thapsigargin, cyclopiazonic acid, caffeine and ryanodine); 4-aminopyridine (A-type K+ current blocker); phospholipase C and adenylyl cyclase pathways blockers U-73122, Rp-cAMP, SQ-22536 and H-89 had no effect. Oscillations were blocked by GABA, but not by glutamate, apamin or dynorphin. In conclusion, spontaneous oscillations in magnocellular neurones are mediated by a concerted action of R-type Ca2+ channels and the NCX fluctuating between forward and reverse modes.
Mots clés
5-Trisphosphate
Tetrodotoxin
Ca2+ channel toxins
Ca2+ signalling
Voltage-gated Ca2+ channels
Ca2+ homeostasis
Ca2+ imaging
Ca2+ oscillations
Ca2+ clearance
Transgenic rats
Vasopressin
Oxytocin
Hypothalamus
Supraoptic nucleus
Na+/Ca2+ exchanger
Mitochondria
Plasma membrane calcium pump
Sarcoendoplasmic reticulum Ca2+-ATPase
GABA
Glutamate
Domaines
NeurobiologieOrigine | Fichiers produits par l'(les) auteur(s) |
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