The role of Ca2+ in the generation of spontaneous astrocytic Ca2+ oscillations

H.R. Parri, V. Crunelli

Research output: Contribution to journalArticle

Abstract

Astrocytes in the rat thalamus display spontaneous [Ca2+]i oscillations that are due to intracellular release, but are not dependent on neuronal activity. In this study we have investigated the mechanisms involved in these spontaneous [Ca2+]i oscillations using slices loaded with Fluo-4 AM (5 μM) and confocal microscopy. Bafilomycin A1 incubation had no effect on the number of spontaneous [Ca2+]i oscillations indicating that they were not dependent on vesicular neurotransmitter release. Oscillations were also unaffected by ryanodine. Phospholipase C (PLC) inhibition decreased the number of astrocytes responding to metabotropic glutamate receptor (mGluR) activation but did not reduce the number of spontaneously active astrocytes, indicating that [Ca2+]i increases are not due to membrane-coupled PLC activation. Spontaneous [Ca2+]i increases were abolished by an IP3 receptor antagonist, whilst the protein kinase C (PKC) inhibitor chelerythrine chloride prolonged their duration, indicating a role for PKC and inositol 1,4,5,-triphosphate receptor activation. BayK8644 increased the number of astrocytes exhibiting [Ca2+]i oscillations, and prolonged the responses to mGluR activation, indicating a possible effect on store-operated Ca2+ entry. Increasing [Ca2+]o increased the number of spontaneously active astrocytes and the number of transients exhibited by each astrocyte. Inhibition of the endoplasmic reticulum Ca2+ ATPase by cyclopiazonic acid also induced [Ca2+]i transients in astrocytes indicating a role for cytoplasmic Ca2+ in the induction of spontaneous oscillations. Incubation with 20 μM Fluo-4 reduced the number of astrocytes exhibiting spontaneous increases.

This study indicates that Ca2+ has a role in triggering Ca2+ release from an inositol 1,4,5,-triphosphate sensitive store in astrocytes during the generation of spontaneous [Ca2+]i oscillations

Original languageEnglish
Pages (from-to)979-992
Number of pages14
JournalNeuroscience
Volume120
Issue number4
Early online date19 Jul 2003
DOIs
Publication statusPublished - 15 Sep 2003

Keywords

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • aniline Compounds
  • animals
  • animals, newborn
  • Anti-Infective agents, local
  • astrocytes
  • boron compounds
  • caffeine
  • calcium
  • calcium channel agonists
  • calcium signaling
  • dioxolanes
  • drug Interactions
  • enzyme inhibitors
  • Methoxyhydroxyphenylglycol
  • microscopy, confocal
  • Patch-Clamp techniques
  • purines
  • rats
  • ryanodine
  • thalamus
  • thimerosal
  • xanthenes
  • Ventrobasal thalamus
  • glia
  • development
  • Thalamocortical

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