Allosteric activation of brain mitochondrial Ca2+ uptake by spermine and by Ca2+: developmental changes.
Kinetic analysis of 45Ca2+ uptake by rat brain mitochondria in Ca2+ - 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid buffers indicated that spermine both increased the apparent affinity for Ca2+ and decreased the cooperativity of uptake. Both effects are consistent with an allosteric activation of uptake by spermine. The stimulating effect of spermine on 45Ca2+ uptake was maximal with mitochondria from postnatal day 10 animals and then steadily decreased with increasing age to reach adult values by approximately 30 postnatal days; this was observed independently of the substrates used to fuel mitochondria. Mitochondrial Ca2+ buffering was also analyzed by use of a Ca2+-selective electrode. Addition of a large bolus of Ca2+ produced a decrease in the subsequent equilibrium extramitochondrial Ca2+ concentration (or a "rebound overshoot") under some conditions. It is proposed that this effect is the result of an allosteric activation of Ca2+ uptake by Ca2+. This effect was slowly reversible, or hysteretic, and was blocked by spermine. The overshoot was increased in the presence of higher concentrations of Mg2+ and was absent when mitochondria were incubated with 0.3 mM Mg2+. 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 45Ca2+ uptake. The data suggest that spermine produces an allosteric activation of Ca2+ uptake by binding to the same regulatory sites that are involved in the Ca2+-induced activation. The results as a whole suggest that spermine could modulate mitochondrial buffering of the intracellular Ca2+ concentration in brain, particularly during the early postnatal period.
Center for the Neurobiology of Learning and Memory, University of California, Irvine.
J R
JR
Jensen
G
G
Lynch
M
M
Baudry
D000375:Aging; D000494:Allosteric Regulation; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000254:growth & development; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013096:Spermine / Q000494:pharmacology*; D013687:Telencephalon / Q000254:growth & development
D013096:Spermine; D002118:Calcium