Aluminum Inhibits the Fast Phase of Voltage‐Dependent Calcium Influx into Synaptosomes

Michael L. Koenig, Richard S. Jope

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Aluminum has been shown to have neurotoxic effects, but the mechanisms by which it acts are not well understood. Because it has been reported that aluminum can interact with Ca2+-binding sites, the possibility that aluminum might interfere with Ca2+ influx into synaptosomes was examined. At concentrations of 50 μM and greater, aluminum significantly inhibited the fast phase (0-1 s) of the voltage-dependent uptake of 45Ca2+ into synaptosomes. Higher concentrations of aluminum also reduced 45Ca2+ uptake measured at 1 s in nondepolarizing media and inhibited the slow phase of 45Ca2+ uptake into synaptosomes whether they were suspended in either low K or high K media. The possibility that aluminum competitively inhibits the fast phase of Ca2+ influx was investigated. Aluminum (250 μM) increased the apparent K(T) (concentration of Ca2+ at which Ca2+ transport is half maximal) for 45Ca2+ of fast phase voltage-dependent channels and slightly decreased the maximal influx (J(max)). These effects are characteristic of a mixed type inhibitor, and the apparent K(i) for Al3+ is estimated to be 0.64 mM. The interaction of aluminum with the fast phase of voltage-dependent calcium influx may disrupt intraneuronal calcium homeostasis and may also represent a means by which aluminum could accumulate intraneuronally.

Original languageEnglish (US)
Pages (from-to)316-320
Number of pages5
JournalJournal of neurochemistry
Volume49
Issue number1
DOIs
StatePublished - Jul 1987

Keywords

  • Aluminum
  • Calcium
  • Neurotoxicity
  • Synaptosome

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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