Change in intracellular pH causes the toxic Ca2+ entry via NCX1 in neuron- and glia-derived cells

Yuji Shono, Masahiro Kamouchi, Takanari Kitazono, Junya Kuroda, Kuniyuki Nakamura, Noriko Hagiwara, Hiroaki Ooboshi, Setsuro Ibayashi, Mitsuo Iida

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14 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)453-460
Number of pages8
JournalCellular and molecular neurobiology
Issue number3
Publication statusPublished - Apr 2010

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

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