Abstract
Mitochondria sequester much of the Ca2+ that enters motor nerve terminals during repetitive stimulation at frequencies exceeding 10-20 Hz. We studied the post-stimulation extrusion of Ca2+ from mitochondria by measuring changes in matrix [Ca2+] with fluorescent indicators loaded into motor terminal mitochondria in the mouse levator auris longus muscle. Trains of action potentials at 50 Hz produced a rapid increase in mitochondrial [Ca2+] followed by a plateau, which was usually maintained after the end of the stimulus train and then slowly decayed back to baseline. Increasing the Ca2+ load delivered to the terminal by increasing the number of stimuli (from 500 to 2000) or the stimulation frequency (from 50 to 100 Hz), by increasing bath [Ca2+], or by prolonging the action potential with 3,4-diaminopyridine (100 μM) prolonged the post-stimulation decay of mitochondrial [Ca2+] without increasing the amplitude of the plateau during stimulation. Inhibiting the opening of the mitochondrial permeability transition pore with cyclosporin A (5 μM) had no significant effect on the decay of mitochondrial [Ca2+]. Inhibition of the mitochondrial Na+-Ca2+ exchanger with CGP-37157 (50 μM) dramatically prolonged the post-stimulation decay of mitochondrial [Ca2+], reduced post-stimulation residual cytosolic [Ca2+], and reduced the amplitude of endplate potentials evoked after the end of a stimulus train in the presence of both low and normal bath [Ca2+]. These findings suggest that Ca2+ extrusion from motor terminal mitochondria occurs primarily via the mitochondrial Na+-Ca2+ exchanger and helps to sustain post-tetanic transmitter release at mouse neuromuscular junctions.
| Original language | English |
|---|---|
| Pages (from-to) | 663-675 |
| Number of pages | 13 |
| Journal | Journal of Physiology |
| Volume | 574 |
| Issue number | 3 |
| DOIs | |
| State | Published - Aug 1 2006 |
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- Physiology
Cite this
Extrusion of Ca2+ from mouse motor terminal mitochondria via a Na+-Ca2+ exchanger increases post-tetanic evoked release. / García-Chacón, Luis E.; Nguyen, Khanh T.; David, Gavriel; Barrett, Ellen.
In: Journal of Physiology, Vol. 574, No. 3, 01.08.2006, p. 663-675.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Extrusion of Ca2+ from mouse motor terminal mitochondria via a Na+-Ca2+ exchanger increases post-tetanic evoked release
AU - García-Chacón, Luis E.
AU - Nguyen, Khanh T.
AU - David, Gavriel
AU - Barrett, Ellen
PY - 2006/8/1
Y1 - 2006/8/1
N2 - Mitochondria sequester much of the Ca2+ that enters motor nerve terminals during repetitive stimulation at frequencies exceeding 10-20 Hz. We studied the post-stimulation extrusion of Ca2+ from mitochondria by measuring changes in matrix [Ca2+] with fluorescent indicators loaded into motor terminal mitochondria in the mouse levator auris longus muscle. Trains of action potentials at 50 Hz produced a rapid increase in mitochondrial [Ca2+] followed by a plateau, which was usually maintained after the end of the stimulus train and then slowly decayed back to baseline. Increasing the Ca2+ load delivered to the terminal by increasing the number of stimuli (from 500 to 2000) or the stimulation frequency (from 50 to 100 Hz), by increasing bath [Ca2+], or by prolonging the action potential with 3,4-diaminopyridine (100 μM) prolonged the post-stimulation decay of mitochondrial [Ca2+] without increasing the amplitude of the plateau during stimulation. Inhibiting the opening of the mitochondrial permeability transition pore with cyclosporin A (5 μM) had no significant effect on the decay of mitochondrial [Ca2+]. Inhibition of the mitochondrial Na+-Ca2+ exchanger with CGP-37157 (50 μM) dramatically prolonged the post-stimulation decay of mitochondrial [Ca2+], reduced post-stimulation residual cytosolic [Ca2+], and reduced the amplitude of endplate potentials evoked after the end of a stimulus train in the presence of both low and normal bath [Ca2+]. These findings suggest that Ca2+ extrusion from motor terminal mitochondria occurs primarily via the mitochondrial Na+-Ca2+ exchanger and helps to sustain post-tetanic transmitter release at mouse neuromuscular junctions.
AB - Mitochondria sequester much of the Ca2+ that enters motor nerve terminals during repetitive stimulation at frequencies exceeding 10-20 Hz. We studied the post-stimulation extrusion of Ca2+ from mitochondria by measuring changes in matrix [Ca2+] with fluorescent indicators loaded into motor terminal mitochondria in the mouse levator auris longus muscle. Trains of action potentials at 50 Hz produced a rapid increase in mitochondrial [Ca2+] followed by a plateau, which was usually maintained after the end of the stimulus train and then slowly decayed back to baseline. Increasing the Ca2+ load delivered to the terminal by increasing the number of stimuli (from 500 to 2000) or the stimulation frequency (from 50 to 100 Hz), by increasing bath [Ca2+], or by prolonging the action potential with 3,4-diaminopyridine (100 μM) prolonged the post-stimulation decay of mitochondrial [Ca2+] without increasing the amplitude of the plateau during stimulation. Inhibiting the opening of the mitochondrial permeability transition pore with cyclosporin A (5 μM) had no significant effect on the decay of mitochondrial [Ca2+]. Inhibition of the mitochondrial Na+-Ca2+ exchanger with CGP-37157 (50 μM) dramatically prolonged the post-stimulation decay of mitochondrial [Ca2+], reduced post-stimulation residual cytosolic [Ca2+], and reduced the amplitude of endplate potentials evoked after the end of a stimulus train in the presence of both low and normal bath [Ca2+]. These findings suggest that Ca2+ extrusion from motor terminal mitochondria occurs primarily via the mitochondrial Na+-Ca2+ exchanger and helps to sustain post-tetanic transmitter release at mouse neuromuscular junctions.
UR - http://www.scopus.com/inward/record.url?scp=33746217838&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746217838&partnerID=8YFLogxK
U2 - 10.1113/jphysiol.2006.110841
DO - 10.1113/jphysiol.2006.110841
M3 - Article
C2 - 16613870
AN - SCOPUS:33746217838
VL - 574
SP - 663
EP - 675
JO - Journal of Physiology
JF - Journal of Physiology
SN - 0022-3751
IS - 3
ER -