Yy. Peng, EFFECTS OF MITOCHONDRION ON CALCIUM TRANSIENTS AT INTACT PRESYNAPTIC TERMINALS DEPEND ON FREQUENCY OF NERVE FIRING, Journal of neurophysiology, 80(1), 1998, pp. 186-195
The rate and the total amount of Ca2+ elevation in the presynaptic ter
minals of bullfrog sympathetic ganglia depend on the firing frequency
of the terminals. Carbonyl cyanide m-chlorophenylhydrazone (CCCP), a m
itochondrial uncoupler, was used for testing whether mitochondrial Ca2
+ uptake is one of the mechanisms that underlie this frequency depende
nce. Fura-2 fluorimetry was used for measurement of intraterminal Ca2. When stimulations of different durations (30 and 1.5 s) and frequenc
ies (4 and 20 Hz) evoked Ca2+ transients with similar peak amplitudes
(264 +/- 22 nM vs. 251 +/- 18 nM, means +/- SE), CCCP augmented the re
sponses to the 4-Hz stimulation 8.9 times more strongly than it did th
e responses to the 20-Hz stimulation (249.7 +/- 81.5% vs. 25.3 +/- 10.
2%). When stimulations delivered at the two frequencies had the same d
urations (1.5, 3, 6, 10, 20, and 30 s), CCCP enlarged the responses to
the 4-Hz stimulations up to 4.2 times more than it did the responses
to the 20-Hz stimulations. When the same number of stimuli (120) was d
elivered at the two frequencies, the effects of CCCP on the responses
evoked by the 4-Hz train were again 6.8 times stronger than its effect
s on the responses to the 20-Hz stimulation. Therefore neither the pea
k amplitudes of the responses nor the durations of the stimulations di
ctated the extent to which the mitochondria modulated the peak [Ca2+](
i). Instead, the extent of the modulation was governed by the frequenc
y of stimulation. Specifically, the less frequent the Ca2+ influx, the
stronger the mitochondrial modulation Also, during nerve firing Ca2release from the ryanodine-sensitive store had a higher potential to i
nfluence the [Ca2+](i) transients than did Ca2+ removal by the mitocho
ndria for the first 6 s of the responses. On cessation of stimulation,
CCCP reduced the initial rapid rate of Ca2+ decay. Thus uptake by the
mitochondria was an important mechanism for Ca2+ removal after repeti
tive firing at the presynaptic terminals.