Effect of a Prolonged Glutamate Challenge on Plasmalemmal Calcium Permeability in Mammalian Central Neurones. Mn2+ as a Tool to Study Calcium Influx Pathways

Boris I. Khodorov, Dmitriy A. Fayuk, Sergey G. Koshelev, Olga V. Vergun, Vsevolod G. Pinelis, Natalya P. Vinskaya, Tatyana P. Storozhevykh, Elena N. Arsenyeva, Leonid G. Khaspekov, Anatoliy P. Lyzhin, Nikolay Isaev, Ilya V. Victorov, Janet M. Dubinsky

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The rate of Mn2+-induced fluorescence quenching (RFQ) was used as a relative measure of plasma membrane Ca2+ permeability (Pca) in fura-2-loaded cultured hippocampal neurons and cerebellar granule cells during and after protracted (15–30 min) glutamate (GLU) treatment. Some limitations of this method were evaluated using a kinetic model of a competitive binding of Mn2+ and Ca2+ to fura-2 in the cell. In parallel experiment a contribution of Ca2+ influx to the cytoplasinic Ca2+ ([Ca2+]i) was repeatedly examined during and following a prolonged GLU challenge by short-duration “low-Ca2+ trials” (50 pM EGTA) and by measurements of 45CaL2+ uptake. Experiments failed to reveal a putative persistent increase in Pca that earlier was thought to underlie Ca2+ overload of the neuron caused by its toxic GLU treatment. By contrast. a sustained increase of [Ca2+], was found to be associated with a progressive decrease in Pca and Ca2+ influx both in the period of GLU application and after its termination. These findings give new evidence in favour of the hypothesis that the CLU-induced Ca2+ overload of the neuron results mainly from an impairment of its Ca2+ extrusion.

Original languageEnglish (US)
Pages (from-to)215-241
Number of pages27
JournalInternational Journal of Neuroscience
Volume88
Issue number42067
DOIs
StatePublished - Jan 1 1996

Keywords

  • Glutamate
  • fluorescence quenching
  • manganese
  • membrane permeability

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