Allosteric activation of brain mitochondrial Ca2+ uptake by spermine and by Ca2+: brain regional differences.
Analysis of the initial rates of 45Ca2+ uptake by rat brain mitochondria in Ca2+-1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid buffers indicated that nontelencephalic mitochondria exhibited both a much less pronounced stimulatory effect of spermine and significantly more hyperbolic kinetics of Ca2+ uptake than telencephalic mitochondria. Nontelencephalic mitochondria were also markedly less susceptible to a Ca2+-induced hysteretic allosteric activation of the Ca2+ uniporter. A new Ca2+ loading procedure, which strikingly illustrates differences in mitochondrial Ca2+ buffering characteristics, is also described. In this procedure, low concentrations of Ca2+ (1, 2, or 5 microM) were repetitively added to mitochondria every 30 s while changes in free Ca2+ concentration were recorded. Spermine induced a marked attenuation of the rise in free Ca2+ level under these conditions. Steady-state rates of Ca2+ uptake were determined by a quantitative analysis of the buffering of repetitive Ca2+ additions, and, again, brain regional differences were qualitatively similar to those observed in the initial rate kinetics; Ca2+ 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 Ca2+ in the absence of spermine. These results also suggest that there is a lag time in the activation of the uniporter by Ca2+, in addition to the hysteresis that has previously been observed in the deactivation of the uniporter.(ABSTRACT TRUNCATED AT 250 WORDS)
Center for the Neurobiology of Learning and Memory, University of California, Irvine.
J R
JR
Jensen
G
G
Lynch
M
M
Baudry
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002132:Calcium Radioisotopes; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity; D051381:Rats; D013096:Spermine / Q000494:pharmacology*; D013687:Telencephalon / Q000378:metabolism
D002132:Calcium Radioisotopes; D013096:Spermine; D002118:Calcium