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Allosteric Activation off Brain Mitochondrial Ca 2+ Uptake by Spermine and by Ca 2+ : Developmental Changes
Author(s) -
Jensen John R.,
Lynch Gary,
Baudry Michel
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb07411.x
Subject(s) - spermine , allosteric regulation , mitochondrion , chemistry , biophysics , stimulation , biochemistry , receptor , biology , endocrinology , enzyme
Kinetic analysis of 45 Ca 2+ uptake by raj brain mitochondria in Ca 2+ ‐l,2‐bis(o‐aminophenoxy)ethane‐ N, N,N′.N ′‐tetraacetic acid buffers indicated that spermine both increased the apparent affinity for Ca 2+ and decreased the cooperativity of uptake. Both effects are consistent with an allosteric activation of uptake by spermine. The stimulating effect of spermine on 45 Ca 2+ uptake was maximal with mitochondria from postnatal day 10 animals and then steadily decreased with increasing age to reach adult values by ∼30 postnatal days; this was observed independently of the substrates used to fuel mitochondria. Mitochondrial Ca 2+ buffering was also analyzed by use of a Ca 2+ ‐selective electrode. Addition of a large bolus of Ca 2+ produced a decrease in the subsequent equilibrium extramitochondrial Ca 2+ concentration (or a “rebound overshoot”) under some conditions. It is proposed that this effect is the result of an allosteric activation of Ca 2+ uptake by Ca 2+ . This effect was slowly reversible, or hysteretic, and was blocked by spermine. The overshoot was increased in the presence of higher concentrations of Mg 2+ and was absent when mitochondria were incubated with 0.3 mM Mg 2+ . It was maximal in mitochondria prepared from early postnatal brain, and changes in the magnitude of the effect during development paralleled those obtained with spermine stimulation of 45 Ca 2+ uptake. The data suggest that spermine produces an allosteric activation of Ca 2+ uptake by binding to the same regulatory sites that are involved in the Ca 2+ ‐induced activation. The results as a whole suggest that spermine could modulate mitochondrial buffering of the intracellular Ca 2+ concentration in brain, particularly during the early postnatal period.