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Glutamate transporter blockade affects Ca(2+) responses in astrocytes.
Neuroscience 2008; 151(1):56-62N

Abstract

Brief pretreatment of astrocytes in culture with glutamate (500 microM 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 microM) and glutamate transport inhibitor, threo-beta-hydroxy-aspartate (200 microM, TBHA) or glutamate (500 microM) 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.

Authors+Show Affiliations

Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18037246

Citation

Padmashri, R, and S K. Sikdar. "Glutamate Transporter Blockade Affects Ca(2+) Responses in Astrocytes." Neuroscience, vol. 151, no. 1, 2008, pp. 56-62.
Padmashri R, Sikdar SK. Glutamate transporter blockade affects Ca(2+) responses in astrocytes. Neuroscience. 2008;151(1):56-62.
Padmashri, R., & Sikdar, S. K. (2008). Glutamate transporter blockade affects Ca(2+) responses in astrocytes. Neuroscience, 151(1), pp. 56-62.
Padmashri R, Sikdar SK. Glutamate Transporter Blockade Affects Ca(2+) Responses in Astrocytes. Neuroscience. 2008 Jan 2;151(1):56-62. PubMed PMID: 18037246.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glutamate transporter blockade affects Ca(2+) responses in astrocytes. AU - Padmashri,R, AU - Sikdar,S K, Y1 - 2007/09/29/ PY - 2007/08/27/received PY - 2007/09/18/revised PY - 2007/09/28/accepted PY - 2007/11/27/pubmed PY - 2008/4/23/medline PY - 2007/11/27/entrez SP - 56 EP - 62 JF - Neuroscience JO - Neuroscience VL - 151 IS - 1 N2 - Brief pretreatment of astrocytes in culture with glutamate (500 microM 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 microM) and glutamate transport inhibitor, threo-beta-hydroxy-aspartate (200 microM, TBHA) or glutamate (500 microM) 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. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/18037246/Glutamate_transporter_blockade_affects_Ca_2+__responses_in_astrocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(07)01218-3 DB - PRIME DP - Unbound Medicine ER -