TY - JOUR
T1 - Mitochondrial clearance of cytosolic Ca2+ in stimulated lizard motor nerve terminals proceeds without progressive elevation of mitochondrial matrix [Ca2+]
AU - David, Gavriel
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1999/9/1
Y1 - 1999/9/1
N2 - This study used fluorescent indicator dyes to measure changes in cytosolic and mitochondrial [Ca2+] produced by physiological stimulation of lizard motor nerve terminals. During repetitive action potential discharge at 10-50 Hz, the increase in average cytosolic [Ca2+] reached plateau at levels that increased with increasing stimulus frequency. This stabilization of cytosolic [Ca2+] was caused mainly by mitochondrial Ca2+ uptake, because drugs that depolarize mitochondria greatly increased the stimulation- induced elevation of cytosolic [Ca2+], whereas blockers of other Ca2+ clearance routes had little effect. Surprisingly, during this sustained Ca2+ uptake the free [Ca2+] in the mitochondrial matrix never exceeded a plateau level of ~1 μM, regardless of stimulation frequency or pattern. When stimulation ceased, matrix [Ca2+] decreased over a slow (~10 min) time course consisting of an initial plateau followed by a return to baseline. These measurements demonstrate that sustained mitochondrial Ca2+ uptake is not invariably accompanied by progressive elevation of matrix free [Ca2+]. Both the plateau of matrix free [Ca2+] during stimulation and its complex decay after stimulation could be accounted for by a model incorporating reversible formation of an insoluble Ca salt. This mechanism allows mitochondria to sequester large amounts of Ca2+ while maintaining matrix free [Ca2+] at levels sufficient to activate Ca2+-dependent mitochondrial dehydrogenases, but below levels that activate the permeability transition pore.
AB - This study used fluorescent indicator dyes to measure changes in cytosolic and mitochondrial [Ca2+] produced by physiological stimulation of lizard motor nerve terminals. During repetitive action potential discharge at 10-50 Hz, the increase in average cytosolic [Ca2+] reached plateau at levels that increased with increasing stimulus frequency. This stabilization of cytosolic [Ca2+] was caused mainly by mitochondrial Ca2+ uptake, because drugs that depolarize mitochondria greatly increased the stimulation- induced elevation of cytosolic [Ca2+], whereas blockers of other Ca2+ clearance routes had little effect. Surprisingly, during this sustained Ca2+ uptake the free [Ca2+] in the mitochondrial matrix never exceeded a plateau level of ~1 μM, regardless of stimulation frequency or pattern. When stimulation ceased, matrix [Ca2+] decreased over a slow (~10 min) time course consisting of an initial plateau followed by a return to baseline. These measurements demonstrate that sustained mitochondrial Ca2+ uptake is not invariably accompanied by progressive elevation of matrix free [Ca2+]. Both the plateau of matrix free [Ca2+] during stimulation and its complex decay after stimulation could be accounted for by a model incorporating reversible formation of an insoluble Ca salt. This mechanism allows mitochondria to sequester large amounts of Ca2+ while maintaining matrix free [Ca2+] at levels sufficient to activate Ca2+-dependent mitochondrial dehydrogenases, but below levels that activate the permeability transition pore.
KW - Calcium buffering
KW - Calcium indicator dyes
KW - Calcium sequestration
KW - Mitochondria
KW - Mitochondrial calcium uptake
KW - Mitochondrial matrix
KW - Motor nerve terminal
KW - Presynaptic terminal
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U2 - 10.1523/jneurosci.19-17-07495.1999
DO - 10.1523/jneurosci.19-17-07495.1999
M3 - Article
C2 - 10460256
AN - SCOPUS:0033198196
VL - 19
SP - 7495
EP - 7506
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 17
ER -