Glutamate transporter blockade affects Ca2+ responses in astrocytes

R. Padmashri, S. K. Sikdar

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Brief pretreatment of astrocytes in culture with glutamate (500 μM for 20 min), was earlier shown to significantly enhance the Ca2+ responses to a depolarizing pulse. It is known that malfunction of glutamate transporters increases extracellular glutamate concentration. We hypothesized that pretreatment of astrocytes with glutamate in conditions where the glutamate transporter activity is blocked should cause further elevation of the Ca2+ responses to a depolarizing pulse. To test the hypothesis we pretreated astrocytes in culture (primary rat astrocyte cultures) with glutamate (500 μM) and glutamate transport inhibitor, threo-β-hydroxy-aspartate (200 μM, TBHA) or glutamate (500 μM) in Na+ free extracellular solution for 20 min. The Ca2+ responses were elicited by depolarization of the astrocyte to evoke voltage-gated Ca2+ currents. Paradoxical attenuation of the Ca2+ transients was observed when the glutamate pretreatment was done in conditions that blocked glutamate transport, accompanied by faster rise and decay times. When the experiments were done on astrocyte pairs that were pretreated with glutamate and TBHA, we observed attenuated Ca2+ responses in the adjoining cell when compared with the depolarized cell. The results were contrary to our earlier observation of heightened responses in the adjoining cell of the astrocyte pair, in cells pretreated with glutamate alone. The attenuated Ca2+ responses in astrocytes would imply decrease in the vesicular release of glutamate and ATP. Extracellular glutamate concentration dependent regulation of the Ca2+ signaling mechanism thus seems to operate in astrocytes, which may be important in regulating the neurotoxic accumulation of glutamate in the extracellular space and the synapse.

Original languageEnglish (US)
Pages (from-to)56-62
Number of pages7
JournalNeuroscience
Volume151
Issue number1
DOIs
StatePublished - Jan 2 2008

Keywords

  • Ca responses
  • astrocytes
  • calcium imaging
  • glutamate
  • glutamate receptors
  • glutamate transporter blockade

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Glutamate transporter blockade affects Ca<sup>2+</sup> responses in astrocytes'. Together they form a unique fingerprint.

  • Cite this