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Allosteric Activation of Brain Mitochondrial Ca 2+ Uptake by Spermine and ty Ca 2+ : Brain Regional Differences
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.tb07412.x
Subject(s) - spermine , uniporter , mitochondrion , allosteric regulation , biophysics , kinetics , chemistry , calcium , stimulation , biochemistry , biology , cytosol , receptor , endocrinology , enzyme , organic chemistry , quantum mechanics , physics
Analysis of the initial rates of 45 Ca 2 1 uptake by rat brain mitochondria in Ca 2+ ‐1,2‐bis(o‐aminophenoxy)ethane‐N, N, N′,N′‐tetraacetic acid buffers indicated t[hat nontelen‐cephalic mitochondria exhibited both a mnch less pronounced stimulatory effect of spermine and signjificantly more hyperbolic kinetics of Ca 2+ uptake than telencjephalic mitochondria. Nontelencephalic mitochondria were also markedly less susceptible to a Ca 2+ ‐induced hysteretic allosteric activation of the Ca 2+ uniporter. A new Ca 2+ loading procedure, which strikingly illustrates differences in mitochondrial Ca 2+ buffering characteristics, is also described. In thjis procedure, low concentrations of Ca 2+ (1, 2, or 5 μ M ) were repetitively added to mitochondria every 30 s while changek in free Ca 2+ concentration were recorded. Spermine induced a marked attenuation of the rise in free Ca 2+ level underj these conditions. Steady‐state rates of Ca 2+ uptake were determined by a quantitative analysis of the buffering of repetitive Ca 2+ additions, and, again, brain regional differences Were qualitatively similar to those observed in the initial rate kinetics; Ca 2+ uptake by nontelencephalic mitochondria in the steady state was markedly less responsive to stimulation by spermine and appeared to have a more hyperbolic dependence on Ca 2 in the absence of spermine. These results also suggested that there is a lag time in the activation of the uniporter by Ca 2+ , in addition to the hysteresis that has previously been observed in the deactivation of the uniporter. In summary, the present results indicate that the Ca 2+ uniporter of nontelencephalic mitochondria is markedly less responsive to allosteric activation by both Ca 2+ and spermine and that this is related to. but not entirely explained by, the more hyperbolic dependence of uptake on Ca 2+ in nontelencephalic mitochondria. It is proposed that mitochondrial buffering of intracellular Ca 2+ and the modulation of this process by spermine differ in telencephalic and nontelencephalic regions of brain.