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The Journal of Neuroscience, September 1, 1999, 19(17):7495-7506
Mitochondrial Clearance of Cytosolic Ca2+ in
Stimulated Lizard Motor Nerve Terminals Proceeds without Progressive
Elevation of Mitochondrial Matrix [Ca2+]
Gavriel
David
Department of Physiology and Biophysics, University of Miami School
of Medicine, Miami Florida 33101
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.
Key words:
mitochondria; mitochondrial calcium uptake; presynaptic terminal; motor nerve terminal; mitochondrial matrix; calcium indicator dyes; calcium buffering; calcium sequestration
Copyright © 1999 Society for Neuroscience 0270-6474/99/19177495-12$05.00/0
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