Na+-Ca2+ exchange activity in central nerve endings. I. Ionic conditions that discriminate 45Ca2+ uptake through the exchanger from that occurring through voltage-operated Ca2+ channels

Maurizio Taglialatela, Gianfranco Di Renzo, Lucio Annunziato

Research output: Contribution to journalArticlepeer-review

Abstract

Ca2+ entrance in central nerve endings can occur through voltage-operated Ca2+ channels and/or through the Na+-Ca2+ antiporter. The aim of the present study was to evaluate, in brain synaptosomes, the possible contribution of these two Ca2+ entrance pathways in the process of 45Ca2+ uptake elicited by different extracellular ionic conditions. The decrease in extracellular Na+ concentration from 145 mM to 95 mM and its concomitant substitution with complemental concentration of K+ (5-55 mM) caused an increase in 45Ca2+ uptake, whereas an equimolar concentration of choline (50 mM), although in the presence of the same Na+ concentration (95 mM), failed to stimulate 45Ca2+ uptake. Only when the extracellular Na+ concentration was further lowered from 95 mM to 0 mM and substituted with equivalent amounts of choline (50-145 mM) did a dose-dependent stimulation of 45Ca2+ uptake occur. In addition, when the lowering of the extracellular Na+ concentration from 95 mM to 0 mM was compensated for by K+ concentrations higher than 55 mM (55-150 mM), 45Ca2+ uptake was higher than that elicited by Na+ ion substitution with equimolar amounts (50-145 mM) of choline. The amount of 45Ca2+ uptake induced by 55 mM K+ did not differ either in Na+-preincubated or in Na+-depleted synaptosomes. Synaptosomal membrane potential, monitored with the potential-sensitive fluorescent dye bis-(1,3-diethyltiobarbiturate)trimethineoxonol, showed a progressive depolarization when extracellular K+ concentrations were raised from 5 to 150 mM, reaching a plateau at 55 mM extracellular K+ concentration, whereas when choline (145 mM) completely substituted for extracellular Na+ ions, synaptosomal membrane potential did not show any depolarization. Collectively, these results demonstrate that 45Ca2+ uptake induced by 55 mM K+ ions occurs selectively through voltage-operated Ca2+ channels, whereas, in choline-substituted media, starting from 70 mM choline, Ca2+ ions seemed to utilize the Na+-Ca2+ antiporter to penetrate into synaptosomes. In contrast, when extracellular K+ concentrations are raised above 55 mM, 45Ca2+ entrance may occur through two cumulative mechanisms, the opening of Ca2+ channels that are activated by high K+-induced depolarization and the activation of the Na+-Ca2+ antiporter, which follows the reduction of the transmembrane Na+ electrochemical gradient. Furthermore, studies on the kinetics of 45Ca2+ uptake induced by 145 mM choline or 55 mM K+ showed significant differences in both Km and Vmax values, suggesting that 45Ca2+ uptake in brain synaptosomes induced by 145 mM choline or 55 mM K+ may occur through pathways characterized by different kinetic parameters. In conclusion, the results of the present experiments suggest that it is possible to selectively promote Ca2+ entrance into brain synaptosomes through voltage-operated Ca2+ channels and/or through the Na+-Ca2+ antiporter, depending on the ionic environment of the extracellular fluid.

Original languageEnglish
Pages (from-to)385-392
Number of pages8
JournalMolecular Pharmacology
Volume38
Issue number3
Publication statusPublished - Sep 1990

ASJC Scopus subject areas

  • Pharmacology

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