Discrepant intracellular pH changes following intracellular Ca2+ increases induced by glutamate and Ca2+ ionophores in rat hippocampal neurons

Masayuki Yamamoto, Toru Kawanishi, Takehito Kiuchi, Miyako Ohta, Isue Yokota, Hisayuki Ohata, Kazutaka Momose, Kazuhide Inoue, Takao Hayakawa

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11 Citations (Scopus)


We investigated changes in intracellular pH (pHi) in relation to intracellular Ca2+ concentration ([Ca2+]i) in primary cultured hippocampal neurons treated with glutamate. [Ca2+]i and phi were imaged with fluorescent dyes and confocal microscopy. Exposure to 1 mM glutamate for 10 min increased [Ca2+]i and evoked acidosis. These changes persisted for at least 60 min, even after removal of glutamate. The increase in [Ca2+]i and the acidosis were not observed in Ca2+-free solution and were attenuated in the presence of MK-801, an NMDA receptor antagonist. We also found that the increase in [Ca2+]i and acidosis could be induced by addition of Ca2+ to the extracellular solution in the cells pretreated with glutamate in Ca2+-free solution, even if glutamate did not exist in the extracellular solution. On the other hand, ionomycin and Br-A23187, calcium ionophores, increased [Ca2+]i to almost the same level as glutamate and increased phi. Extracellular Ca2+ was also indispensable for the increase in [Ca2+]i and the alkalosis. These results suggest the followings: 1) intracellular acidosis by glutamate is dependent on the presence of extracellular Ca2+; 2) the acidosis does not result from only the increase in [Ca2+]i; and 3) glutamate induces the irreversible disorder of regulatory mechanisms of [Ca2+]i not only by Ca2+-dependent process, but also by Ca2+-independent process.

Original languageEnglish
Pages (from-to)55-63
Number of pages9
JournalLife Sciences
Issue number1
Publication statusPublished - May 29 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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