Abstract
Brain hypoxia or ischemia causes acidosis and the intracellular accumulation of Ca2+ in neuron. The aims of the present study were to elucidate the interaction between intracellular pH and Ca2+ during transient acidosis and its effects on the viability of neuronal and glial cells. Intracellular Ca2+ and pH were measured using the fluorescence of fura-2 and 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester in neuroblastoma (IMR-32), glioblastoma (T98G), and astrocytoma (CCF-STTG1) cell lines. The administration of 5 mM propionate caused intracellular acidification in IMR-32 and T98G cells but not in CCF-STTG1 cells. After the removal of propionate, the intracellular pH recovered to the resting level. The intracellular Ca2+ transiently increased upon the removal of propionate in IMR-32 and T98G cells but not in CCF-STTG1 cells. The transient Ca2+ increase caused by the withdrawal of intracellular acidification was abolished by the removal of external Ca2+, diminished by a reduction of external Na+, and inhibited by benzamil. Transient acidosis caused cell death, whereas the cells were more viable in the absence of external Ca2+. Benzamil alleviated cell death caused by transient acidosis in IMR-32 and T98G cells but not in CCF-STTG1 cells. These results suggest that recovery from intracellular acidosis causes a transient increase in cytosolic Ca2+ due to reversal of Ca2+ transport via Na+/Ca2+ exchanger coactivated with Na+/H+ exchanger, which can cause cell death.
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This work was supported by a Grand-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (C 19590992). We are grateful to the Cell Resource Center for Biomedical Research, Tohoku University for donating the cell lines.
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Shono, Y., Kamouchi, M., Kitazono, T. et al. Change in Intracellular pH Causes the Toxic Ca2+ Entry via NCX1 in Neuron- and Glia-Derived Cells. Cell Mol Neurobiol 30, 453–460 (2010). https://doi.org/10.1007/s10571-009-9470-7
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DOI: https://doi.org/10.1007/s10571-009-9470-7