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H2O2 Mobilizes Ca2+ from Agonist- and Thapsigargin-sensitive and Insensitive Intracellular Stores and Stimulates Glutamate Secretion in Rat Hippocampal Astrocytes

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Abstract

The effect of hydrogen peroxide (H2O2) on cytosolic free calcium concentration ([Ca2+]c) as well as its effect on glutamate secretion in rat hippocampal astrocytes have been the aim of the present research. Our results show that 100 μM H2O2 induces an increase in [Ca2+]c, that remains at an elevated level while the oxidant is present in the perfusion medium, due to its release from intracellular stores as it was observed in the absence of extracellular Ca2+, followed by a significant increase in glutamate secretion. Ca2+-mobilization in response to the oxidant could only be reduced by thapsigargin plus FCCP, indicating that the Ca2+-mobilizable pool by H2O2 includes both endoplasmic reticulum and mitochondria. We conclude that ROS in hippocampal astrocytes might contribute to an elevation of resting [Ca2+]c which, in turn, could lead to a maintained secretion of the excitatory neurotransmitter glutamate, which has been considered a situation potentially leading to neurotoxicity in the hippocampus.

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Acknowledgements

This work was supported by Junta de Extremadura-Consejería de Educación, Ciencia y Tecnología (2PR04A009). María P. Granados is supported by a grant from Consejería de Educación, Ciencia y Tecnología-Junta de Extremadura y Fondo Social Europeo (FIC02A022). The authors would like to thank Dr. Rafael Fernández Chacón and Mr. Pablo García-Junco Clemente from the Faculty of Medicine of the University of Sevilla for their valuable criticisms and help in preparing the cell cultures, and Mrs. Mercedes Gómez Blázquez, from the Department of Physiology of the University of Extremadura, for her technical assistance.

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  1. Department of Physiology, University of Extremadura, Avenida Universidad s/n, E-10071, Cáceres, Spain

    Antonio González, María P. Granados, José A. Pariente & Ginés M. Salido

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  1. Antonio González
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  2. María P. Granados
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  3. José A. Pariente
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  4. Ginés M. Salido
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Correspondence to Antonio González.

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González, A., Granados, M.P., Pariente, J.A. et al. H2O2 Mobilizes Ca2+ from Agonist- and Thapsigargin-sensitive and Insensitive Intracellular Stores and Stimulates Glutamate Secretion in Rat Hippocampal Astrocytes. Neurochem Res 31, 741–750 (2006). https://doi.org/10.1007/s11064-006-9078-y

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  • DOI: https://doi.org/10.1007/s11064-006-9078-y

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