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Glutamate transporter blockade affects $Ca^{2+}$ responses in astrocytes

Padmashri, R and Sikdar, SK (2008) Glutamate transporter blockade affects $Ca^{2+}$ responses in astrocytes. In: Neuroscience, 151 (1). pp. 56-62.

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Brief pretreatment of astrocytes in culture with glutamate (500 \mu M for 20 min), was earlier shown to significantly enhance the $Ca^{2+}$ 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 $Ca^{2+}$ responses to a depolarizing pulse. To test the hypothesis we pretreated astrocytes in culture (primary rat astrocyte cultures) with glutamate (500 \mu M) and glutamate transport inhibitor, threo-\beta-hydroxy-aspartate (200 \mu M, TBHA) or glutamate (500 \mu M) in $Na^{+}$ free extracellular solution for 20 min. The $Ca^{2+}$ responses were elicited by depolarization of the astrocyte to evoke voltage-gated $Ca^{2+}$ currents. Paradoxical attenuation of the $Ca^{2+}$ 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 $Ca^{2+}$ 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 $Ca^{2+}$ responses in astrocytes would imply decrease in the vesicular release of glutamate and ATP. Extracellular glutamate concentration dependent regulation of the $Ca^{2+}$ 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.

Item Type: Journal Article
Publication: Neuroscience
Publisher: Elsevier
Additional Information: Copyright of this article belongs to Elsevier.
Keywords: astrocytes;Ca2+ responses;glutamate;glutamate transporter blockade;glutamate receptors;calcium imaging.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 31 Jul 2008
Last Modified: 19 Sep 2010 04:48
URI: http://eprints.iisc.ac.in/id/eprint/15390

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