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) All Versions of this Article: 548/2/425    most recent 2002.035196v1 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.

Mitochondrial Ca²⁺ uptake prevents desynchronization of quantal release and minimizes depletion during repetitive stimulation of mouse motor nerve terminals

Gavriel David and Ellen F. Barrett

We investigated how inhibition of mitochondrial Ca²⁺ uptake affects transmitter release from mouse motor terminals during brief trains of action potentials (500 at 50 Hz) in physiological bath [Ca²⁺]. When mitochondrial Ca²⁺ uptake was inhibited by depolarizing mitochondria with antimycin A1 or carbonyl cyanide m-chlorophenyl-hydrazone, the stimulation-induced increase in cytosolic [Ca²⁺] was greater (> 10 µM, compared to 1µM in control solution), the quantal content of the endplate potential (EPP) depressed more rapidly (~84 % depression compared to ~8 % in controls), and asynchronous release during the stimulus train reached higher frequencies (peak rates of ~6000 s^-1 compared to ~75 s^-1 in controls). These effects of mitochondrial depolarization were not accompanied by a significant change in EPP quantal content or the rate of asynchronous release during 1 Hz stimulation, and were not seen in oligomycin, which blocks mitochondrial ATP synthesis without depolarizing mitochondria. Inhibition of endoplasmic reticular Ca²⁺ uptake with cyclopiazonic acid also had little effect on stimulation-induced changes in cytosolic [Ca²⁺] or EPP amplitude. We hypothesize that the high rate of asynchronous release evoked by stimulation during mitochondrial depolarization was produced by the elevation of cytosolic [Ca²⁺], and contributed to the accelerated depression of phasic release by reducing the availability of releasable vesicles. During mitochondrial depolarization, the post-tetanic potentiation of the EPP observed under control conditions was replaced by a post-tetanic depression with a slow time course of recovery. Thus, mitochondrial Ca²⁺ uptake is essential for sustaining phasic release, and thus neuromuscular transmission, during and following tetanic stimulation.

This article has been cited by other articles:

				K. J. Iremonger and J. S. Bains Integration of Asynchronously Released Quanta Prolongs the Postsynaptic Spike Window J. Neurosci., June 20, 2007; 27(25): 6684 - 6691. [Abstract] [Full Text] [PDF]

				M. Avissar, A. C. Furman, J. C. Saunders, and T. D. Parsons Adaptation Reduces Spike-Count Reliability, But Not Spike-Timing Precision, of Auditory Nerve Responses J. Neurosci., June 13, 2007; 27(24): 6461 - 6472. [Abstract] [Full Text] [PDF]

				L. Nunez, L. Senovilla, S. Sanz-Blasco, P. Chamero, M. T. Alonso, C. Villalobos, and J. Garcia-Sancho Bioluminescence imaging of mitochondrial Ca2+ dynamics in soma and neurites of individual adult mouse sympathetic neurons J. Physiol., April 15, 2007; 580(2): 385 - 395. [Abstract] [Full Text] [PDF]

				O. Kann and R. Kovacs Mitochondria and neuronal activity Am J Physiol Cell Physiol, February 1, 2007; 292(2): C641 - C657. [Abstract] [Full Text] [PDF]

				C. V. Ly and P. Verstreken Mitochondria at the Synapse Neuroscientist, August 1, 2006; 12(4): 291 - 299. [Abstract] [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]

				D. T. W. Chang, A. S. Honick, and I. J. Reynolds Mitochondrial trafficking to synapses in cultured primary cortical neurons. J. Neurosci., June 28, 2006; 26(26): 7035 - 7045. [Abstract] [Full Text] [PDF]

				M. R. Pagani, R. C. Reisin, and O. D. Uchitel Calcium signaling pathways mediating synaptic potentiation triggered by amyotrophic lateral sclerosis IgG in motor nerve terminals. J. Neurosci., March 8, 2006; 26(10): 2661 - 2672. [Abstract] [Full Text] [PDF]

				E.-L. Belair, J. Vallee, and R. Robitaille Long-term in vivo modulation of synaptic efficacy at the neuromuscular junction of Rana pipiens frogs J. Physiol., November 15, 2005; 569(1): 163 - 178. [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]