Extracellular acidification modifies Ca2+ fluxes in rat brain synaptosomes

Samira Saadoun, Mónica Lluch, José Rodríguez-Álvarez, Isaac Blanco, Ricardo Rodríguez

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

We examined the influence of external acidification on Ca2+ fluxes (45Ca2+ influx and 45Ca2+ efflux) in rat brain synaptosomes. A change on external pH (pH(e)) from 7.5 to 6.5 linearly decreased the 45Ca2+ uptake (5 nmoles/mg protein/pH unit) and increased the 45Ca2+ efflux (1.5 fold/pH unit). These changes were both Na+ dependent and amiloride sensitive suggesting that the Na+/Ca2+ exchanger could be involved. The addition of the Ca2+ channel blockers (diltiazem, verapamil, nifedipine) did not prevent the decrease of the 45Ca2+ uptake evoked by acid pH, and so the involvement of the voltage-sensitive Ca2+ channels could be discarded. In order to determine whether the Na+/Ca2+ exchanger was directly activated by H+ or was indirectly activated by an internal mobilization of Ca2+ from intrasynaptosomal stores we examined the effect of pH(e) variation on phophoinositide hydrolisis. An increase on phosphoinositide hydrolisis was observed at acid pH(e) values (7 and 6.5). The hydrolisis was amiloride insensitive, On the other hand 1 mM neomycin did inhibit the effect of acidic pH(e) on Ca2+ fluxes. Taken together, the results of our study provide evidence that external acidification stimulates phospholipase C leading to an increase in phosphoinositide hydrolisis and Ca2+ mobilization. The increase in intracellular Ca2+ would stimulate the Na+/Ca2+ exchanger, increasing Ca2+ efflux and reducing the global Ca2+ influx.
Original languageEnglish
Pages (from-to)123-128
JournalBiochemical and Biophysical Research Communications
Volume242
DOIs
Publication statusPublished - 6 Jan 1998

Keywords

  • Acidification
  • Ca fluxes 2+
  • External pH
  • Na /Ca exchanger + 2+
  • Phosphoinositide hydrolisis
  • Synaptosomes
  • Voltage sensitive calcium channels

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