HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by David, G. Articles by Barrett, E. F. Search for Related Content PubMed PubMed Citation Articles by David, G. Articles by Barrett, E. F.

Evidence that mitochondria buffer physiological Ca²⁺ loads in lizard motor nerve terminals

Gavriel David, John N. Barrett and Ellen F. Barrett

1. Changes in cytosolic and mitochondrial [Ca²⁺] produced by brief trains of action potentials were measured in motor nerve terminals using a rapidly scanning confocal microscope. Cytosolic [Ca²⁺] was measured using ionophoretically injected Oregon Green BAPTA 5N (OG-5N). Mitochondrial [Ca²⁺] was measured using rhod-2, bath loaded as dihydrorhod-2.

2. In response to 100-250 stimuli at 25-100 Hz the average cytosolic [Ca²⁺] showed an initial rapid increase followed by a much slower rate of increase. Mitochondrial [Ca²⁺] showed no detectable increase during the first fifteen to twenty stimuli, but after this initial delay also showed an initially rapid rise followed by a slower rate of increase. The onset of the increase in mitochondrial [Ca²⁺] coincided with the slowing of the rate of rise of cytosolic [Ca²⁺]. The peak levels of cytosolic and mitochondrial [Ca²⁺] both increased with increasing frequencies of stimulation.

3. When stimulation terminated, the initial rate of decay of cytosolic [Ca²⁺] was much more rapid than that of mitochondrial [Ca²⁺].

4. After addition of carbonyl cyanide m-chlorophenyl hydrazone (CCCP, 1-2 µM) to dissipate the proton electrochemical gradient across the mitochondrial membrane, cytosolic [Ca²⁺] rose rapidly throughout the stimulus train, reaching levels much higher than normal. CCCP inhibited the increase in mitochondrial [Ca²⁺].

5. These results suggest that mitochondrial uptake of Ca²⁺ contributes importantly to buffering presynaptic cytosolic [Ca²⁺] during normal neuromuscular transmission.

This article has been cited by other articles:

				M. E. Quinlan, C. O. Alberto, and M. Hirasawa Short-term potentiation of mEPSCs requires N-, P/Q- and L-type Ca2+ channels and mitochondria in the supraoptic nucleus J. Physiol., July 1, 2008; 586(13): 3147 - 3161. [Abstract] [Full Text] [PDF]

				Y. V. Medvedeva, M.-S. Kim, and Y. M. Usachev Mechanisms of Prolonged Presynaptic Ca2+ Signaling and Glutamate Release Induced by TRPV1 Activation in Rat Sensory Neurons J. Neurosci., May 14, 2008; 28(20): 5295 - 5311. [Abstract] [Full Text] [PDF]

				G. Szabadkai and M. R. Duchen Mitochondria: The Hub of Cellular Ca2+ Signaling Physiology, April 1, 2008; 23(2): 84 - 94. [Abstract] [Full Text] [PDF]

				D. Lee, K.-H. Lee, W.-K. Ho, and S.-H. Lee Target Cell-Specific Involvement of Presynaptic Mitochondria in Post-Tetanic Potentiation at Hippocampal Mossy Fiber Synapses J. Neurosci., December 12, 2007; 27(50): 13603 - 13613. [Abstract] [Full Text] [PDF]

				J. Talbot, J. N. Barrett, E. F. Barrett, and G. David Stimulation-induced changes in NADH fluorescence and mitochondrial membrane potential in lizard motor nerve terminals J. Physiol., March 15, 2007; 579(3): 783 - 798. [Abstract] [Full Text] [PDF]

				M. Kubota, T. Kasahara, T. Nakamura, M. Ishiwata, T. Miyauchi, and T. Kato Abnormal Ca2+ Dynamics in Transgenic Mice with Neuron-Specific Mitochondrial DNA Defects. J. Neurosci., November 22, 2006; 26(47): 12314 - 12324. [Abstract] [Full Text] [PDF]

				L. E. Garcia-Chacon, K. T. Nguyen, G. David, and E. F. Barrett Extrusion of Ca2+ from mouse motor terminal mitochondria via a Na+-Ca2+ exchanger increases post-tetanic evoked release J. Physiol., August 1, 2006; 574(3): 663 - 675. [Abstract] [Full Text] [PDF]

				R. Rizzuto and T. Pozzan Microdomains of Intracellular Ca2+: Molecular Determinants and Functional Consequences Physiol Rev, January 1, 2006; 86(1): 369 - 408. [Abstract] [Full Text] [PDF]

				F. H. Andrade, C. A. McMullen, and R. E. Rumbaut Mitochondria Are Fast Ca2+ Sinks in Rat Extraocular Muscles: A Novel Regulatory Influence on Contractile Function and Metabolism Invest. Ophthalmol. Vis. Sci., December 1, 2005; 46(12): 4541 - 4547. [Abstract] [Full Text] [PDF]

				H. Teng and R. S Wilkinson Clathrin-mediated endocytosis in snake motor terminals is directly facilitated by intracellular Ca2+ J. Physiol., June 15, 2005; 565(3): 743 - 750. [Abstract] [Full Text] [PDF]

				M. R. Bennett, L. Farnell, and W. G. Gibson The Facilitated Probability of Quantal Secretion within an Array of Calcium Channels of an Active Zone at the Amphibian Neuromuscular Junction Biophys. J., May 1, 2004; 86(5): 2674 - 2690. [Abstract] [Full Text] [PDF]

				R. Rizzuto, M. R. Duchen, and T. Pozzan Flirting in Little Space: The ER/Mitochondria Ca2+ Liaison Sci. Signal., January 13, 2004; 2004(215): re1 - re1. [Abstract] [Full Text] [PDF]

				R. Rizzuto Calcium mobilization from mitochondria in synaptic transmitter release J. Cell Biol., November 10, 2003; 163(3): 441 - 443. [Abstract] [Full Text] [PDF]

				F. Yang, X.-p. He, J. Russell, and B. Lu Ca2+ influx-independent synaptic potentiation mediated by mitochondrial Na+-Ca2+ exchanger and protein kinase C J. Cell Biol., November 10, 2003; 163(3): 511 - 523. [Abstract] [Full Text] [PDF]

				J. D. Talbot, G. David, and E. F. Barrett Inhibition of Mitochondrial Ca2+ Uptake Affects Phasic Release From Motor Terminals Differently Depending on External [Ca2+] J Neurophysiol, July 1, 2003; 90(1): 491 - 502. [Abstract] [Full Text] [PDF]

				N. Rumpal and G. A. Lnenicka Ca2+ Clearance at Growth Cones Produced by Crayfish Motor Axons in an Explant Culture J Neurophysiol, June 1, 2003; 89(6): 3225 - 3234. [Abstract] [Full Text] [PDF]

				N. B. Pivovarova, L. D. Pozzo-Miller, J. Hongpaisan, and S. B. Andrews Correlated Calcium Uptake and Release by Mitochondria and Endoplasmic Reticulum of CA3 Hippocampal Dendrites after Afferent Synaptic Stimulation J. Neurosci., December 15, 2002; 22(24): 10653 - 10661. [Abstract] [Full Text] [PDF]

				B. Billups and I. D. Forsythe Presynaptic Mitochondrial Calcium Sequestration Influences Transmission at Mammalian Central Synapses J. Neurosci., July 15, 2002; 22(14): 5840 - 5847. [Abstract] [Full Text] [PDF]

				E. J. Weeber, M. Levy, M. J. Sampson, K. Anflous, D. L. Armstrong, S. E. Brown, J. D. Sweatt, and W. J. Craigen The Role of Mitochondrial Porins and the Permeability Transition Pore in Learning and Synaptic Plasticity J. Biol. Chem., May 17, 2002; 277(21): 18891 - 18897. [Abstract] [Full Text] [PDF]

				S. Suzuki, M. Osanai, N. Mitsumoto, T. Akita, K. Narita, H. Kijima, and K. Kuba Ca2+-Dependent Ca2+ Clearance Via Mitochondrial Uptake and Plasmalemmal Extrusion in Frog Motor Nerve Terminals J Neurophysiol, April 1, 2002; 87(4): 1816 - 1823. [Abstract] [Full Text] [PDF]

				K. Medler and E. L. Gleason Mitochondrial Ca2+ Buffering Regulates Synaptic Transmission Between Retinal Amacrine Cells J Neurophysiol, March 1, 2002; 87(3): 1426 - 1439. [Abstract] [Full Text] [PDF]

				N. Zhong, V. Beaumont, and R. S. Zucker Roles for Mitochondrial and Reverse Mode Na+/Ca2+ Exchange and the Plasmalemma Ca2+ ATPase in Post-Tetanic Potentiation at Crayfish Neuromuscular Junctions J. Neurosci., December 15, 2001; 21(24): 9598 - 9607. [Abstract] [Full Text] [PDF]

				K. C. Rowland, N. K. Irby, and G. A. Spirou Specialized Synapse-Associated Structures within the Calyx of Held J. Neurosci., December 15, 2000; 20(24): 9135 - 9144. [Abstract] [Full Text] [PDF]

				C. W. Tsang, D. B. Elrick, and M. P. Charlton alpha -Latrotoxin Releases Calcium in Frog Motor Nerve Terminals J. Neurosci., December 1, 2000; 20(23): 8685 - 8692. [Abstract] [Full Text] [PDF]

				G. David and E. F. Barrett Stimulation-Evoked Increases in Cytosolic [Ca2+] in Mouse Motor Nerve Terminals Are Limited by Mitochondrial Uptake and Are Temperature-Dependent J. Neurosci., October 1, 2000; 20(19): 7290 - 7296. [Abstract] [Full Text] [PDF]

				S. Bahar, D. Fayuk, G. G. Somjen, P. G. Aitken, and D. A. Turner Mitochondrial and Intrinsic Optical Signals Imaged During Hypoxia and Spreading Depression in Rat Hippocampal Slices J Neurophysiol, July 1, 2000; 84(1): 311 - 324. [Abstract] [Full Text] [PDF]

				S. Schuchmann, M. Luckermann, A. Kulik, U. Heinemann, and K. Ballanyi Ca2+- and Metabolism-Related Changes of Mitochondrial Potential in Voltage-Clamped CA1 Pyramidal Neurons In Situ J Neurophysiol, March 1, 2000; 83(3): 1710 - 1721. [Abstract] [Full Text] [PDF]

				D. G. Nicholls and S. L. Budd Mitochondria and Neuronal Survival Physiol Rev, January 1, 2000; 80(1): 315 - 360. [Abstract] [Full Text] [PDF]

				N. Melamed-Book, S. G. Kachalsky, I. Kaiserman, and R. Rahamimoff Neuronal calcium sparks and intracellular calcium "noise" PNAS, December 21, 1999; 96(26): 15217 - 15221. [Abstract] [Full Text] [PDF]

				D. R. Giovannucci, M. D. Hlubek, and E. L. Stuenkel Mitochondria Regulate the Ca2+-Exocytosis Relationship of Bovine Adrenal Chromaffin Cells J. Neurosci., November 1, 1999; 19(21): 9261 - 9270. [Abstract] [Full Text] [PDF]

				G. David Mitochondrial Clearance of Cytosolic Ca2+ in Stimulated Lizard Motor Nerve Terminals Proceeds without Progressive Elevation of Mitochondrial Matrix [Ca2+] J. Neurosci., September 1, 1999; 19(17): 7495 - 7506. [Abstract] [Full Text] [PDF]

				N. B. Pivovarova, J. Hongpaisan, S. B. Andrews, and D. D. Friel Depolarization-Induced Mitochondrial Ca Accumulation in Sympathetic Neurons: Spatial and Temporal Characteristics J. Neurosci., August 1, 1999; 19(15): 6372 - 6384. [Abstract] [Full Text] [PDF]

				A. Meir, S. Ginsburg, A. Butkevich, S. G. Kachalsky, I. Kaiserman, R. Ahdut, S. Demirgoren, and R. Rahamimoff Ion Channels in Presynaptic Nerve Terminals and Control of Transmitter Release Physiol Rev, July 1, 1999; 79(3): 1019 - 1088. [Abstract] [Full Text] [PDF]

				H. Cheng and M. D. Miyamoto Effect of Hypertonicity on Augmentation and Potentiation and on Corresponding Quantal Parameters of Transmitter Release J Neurophysiol, March 1, 1999; 81(3): 1428 - 1431. [Abstract] [Full Text] [PDF]

				A. Gonzalez, I. Schulz, and A. Schmid Agonist-evoked Mitochondrial Ca2+ Signals in Mouse Pancreatic Acinar Cells J. Biol. Chem., December 1, 2000; 275(49): 38680 - 38686. [Abstract] [Full Text] [PDF]