Synaptic Vesicles Control the Time Course of Neurotransmitter Secretion Via a Ca²+/H+ Antiport

Overview

Journal J Physiol

Specialty Physiology

Date 2010 Nov 10

PMID 21059764

Citations 5

Authors

J Miguel Cordeiro

Paula P Goncalves

Yves Dunant

Affiliations

Soon will be listed here.

Abstract

We investigated the physiological role of the vesicular Ca2+/H+ antiport in rapid synaptic transmission using the Torpedo electric organ (a modified neuromuscular system). By inhibiting V-type H+-transporting ATPase (V-ATPase), bafilomycin A1 dissipates the H+ gradient of synaptic vesicles, thereby abolishing the Ca2+/H+ antiport driving force. In electrophysiology experiments, bafilomycin A1 significantly prolonged the duration of the evoked electroplaque potential. A biochemical assay for acetylcholine (ACh) release showed that the effect of bafilomycin A1 was presynaptic. Indeed, bafilomycin A1 increased the amount of radio-labelled ACh released in response to paired-pulse stimulation. Bafilomycin A1 also enhanced Ca2+-dependent ACh release from isolated nerve terminals (synaptosomes). The bafilomycin-induced electroplaque potential lengthening did not arise from cholinesterase inhibition, since eserine (which also prolonged the electroplaque potential) strongly decreased evoked ACh release. Bafilomycin A1 augmented the amount of calcium accumulating in nerve terminals following a short tetanic stimulation and delayed subsequent calcium extrusion. By reducing stimulation-dependent calcium accumulation in synaptic vesicles, bafilomycin A1 diminished the corresponding depletion of vesicular ACh, as tested using both intact tissue and isolated synaptic vesicles. Strontium ions inhibit the vesicular Ca2+/H+ antiport, while activating transmitter release at concentrations one order of magnitude higher than Ca2+ does. In the presence of Sr2+ the time course of the electroplaque potential was also prolonged but, unlike bafilomycin A1, Sr2+ enhanced facilitation in paired-pulse experiments. It is therefore proposed that the vesicular Ca2+/H+ antiport function is to shorten 'phasic' transmitter release, allowing the synapse to transmit briefer impulses and so to work at higher frequencies.

Citing Articles

Opposite Pathways of Cholinergic Mechanisms of Hypoxic Preconditioning in the Hippocampus: Participation of Nicotinic α7 Receptors and Their Association with the Baseline Level of Startle Prepulse Inhibition.

Zakharova E, Storozheva Z, Proshin A, Monakov M, Dudchenko A Brain Sci. 2020; 11(1).

PMID: 33374246 PMC: 7824639. DOI: 10.3390/brainsci11010012.

Ultrafast and Slow Cholinergic Transmission. Different Involvement of Acetylcholinesterase Molecular Forms.

Dunant Y, Gisiger V Molecules. 2017; 22(8).

PMID: 28777299 PMC: 6152031. DOI: 10.3390/molecules22081300.

Association of soil selenium, strontium, and magnesium concentrations with Parkinson's disease mortality rates in the USA.

Sun H Environ Geochem Health. 2017; 40(1):349-357.

PMID: 28176196 DOI: 10.1007/s10653-017-9915-8.

Activation of a TRP-like channel and intracellular Ca2+ dynamics during phospholipase-C-mediated cell death.

Goncalves A, Cordeiro J, Monteiro J, Munoz A, Correia-de-Sa P, Read N J Cell Sci. 2014; 127(Pt 17):3817-29.

PMID: 25037570 PMC: 4150065. DOI: 10.1242/jcs.152058.

Presynaptic K(+) channels, vesicular Ca(2+)/H (+) antiport--synaptotagmin, and acetylcholinesterase, three mechanisms cutting short the cholinergic signal at neuromuscular and nerve-electroplaque junctions.

Dunant Y, Cordeiro J J Mol Neurosci. 2014; 53(3):377-86.

PMID: 24390960 DOI: 10.1007/s12031-013-0212-4.

References

Sabatini B, Regehr W . Timing of neurotransmission at fast synapses in the mammalian brain. Nature. 1996; 384(6605):170-2. DOI: 10.1038/384170a0. View

Sanchez-Prieto J, Sihra T, Nicholls D . Characterization of the exocytotic release of glutamate from guinea-pig cerebral cortical synaptosomes. J Neurochem. 1987; 49(1):58-64. DOI: 10.1111/j.1471-4159.1987.tb03394.x. View

Dunant Y, Gautron J, Israel M, Lesbats B, Manaranche R . [Acetylcholine compartments in stimulated electric organ of Torpedo marmorata]. J Neurochem. 1972; 19(8):1987-2002. DOI: 10.1111/j.1471-4159.1972.tb01488.x. View

Di Giovanni J, Boudkkazi S, Mochida S, Bialowas A, Samari N, Leveque C . V-ATPase membrane sector associates with synaptobrevin to modulate neurotransmitter release. Neuron. 2010; 67(2):268-79. DOI: 10.1016/j.neuron.2010.06.024. View

Goda Y, Stevens C . Two components of transmitter release at a central synapse. Proc Natl Acad Sci U S A. 1994; 91(26):12942-6. PMC: 45556. DOI: 10.1073/pnas.91.26.12942. View

Dodge Jr F, Miledi R, Rahamimoff R . Strontium and quantal release of transmitter at the neuromuscular junction. J Physiol. 1969; 200(1):267-83. PMC: 1350428. DOI: 10.1113/jphysiol.1969.sp008692. View

Cordeiro J, Dunant Y, Goncalves P . Vesicular calcium transport shapes rapid acetylcholine secretion. J Mol Neurosci. 2006; 30(1-2):41-4. DOI: 10.1385/JMN:30:1:41. View

Katz B, Miledi R . Tetrodotoxin-resistant electric activity in presynaptic terminals. J Physiol. 1969; 203(2):459-87. PMC: 1351456. DOI: 10.1113/jphysiol.1969.sp008875. View

Desai-Shah M, Cooper R . Different mechanisms of Ca2+ regulation that influence synaptic transmission: comparison between crayfish and Drosophila neuromuscular junctions. Synapse. 2009; 63(12):1100-21. DOI: 10.1002/syn.20695. View

10.

Llinas R, Steinberg I, Walton K . Relationship between presynaptic calcium current and postsynaptic potential in squid giant synapse. Biophys J. 1981; 33(3):323-51. PMC: 1327434. DOI: 10.1016/S0006-3495(81)84899-0. View

11.

Kishimoto T, Liu T, Ninomiya Y, Takagi H, Yoshioka T, Miyashita Y . Ion selectivities of the Ca(2+) sensors for exocytosis in rat phaeochromocytoma cells. J Physiol. 2001; 533(Pt 3):627-37. PMC: 2278662. DOI: 10.1111/j.1469-7793.2001.t01-1-00627.x. View

12.

Israel M, Meunier F, Morel N, Lesbats B . Calcium-induced desensitization of acetylcholine release from synaptosomes or proteoliposomes equipped with mediatophore, a presynaptic membrane protein. J Neurochem. 1987; 49(3):975-82. DOI: 10.1111/j.1471-4159.1987.tb00989.x. View

13.

Dunant Y . Quantal acetylcholine release: vesicle fusion or intramembrane particles?. Microsc Res Tech. 2000; 49(1):38-46. DOI: 10.1002/(SICI)1097-0029(20000401)49:1<38::AID-JEMT5>3.0.CO;2-0. View

14.

Correges P, Eder-Colli L, Salem N, Roulet E, Bloc A, Meunier F . Quantal acetylcholine release induced by mediatophore transfection. Proc Natl Acad Sci U S A. 1996; 93(11):5203-7. PMC: 39222. DOI: 10.1073/pnas.93.11.5203. View

15.

Cousin M, Nicholls D . Synaptic vesicle recycling in cultured cerebellar granule cells: role of vesicular acidification and refilling. J Neurochem. 1998; 69(5):1927-35. DOI: 10.1046/j.1471-4159.1997.69051927.x. View

16.

Israel M, Lesbats B . Continuous determination by a chemiluminescent method of acetylcholine release and compartmentation in Torpedo electric organ synaptosomes. J Neurochem. 1981; 37(6):1475-83. DOI: 10.1111/j.1471-4159.1981.tb06317.x. View

17.

Lee A, Wong S, Gallagher D, Li B, Storm D, Scheuer T . Ca2+/calmodulin binds to and modulates P/Q-type calcium channels. Nature. 1999; 399(6732):155-9. DOI: 10.1038/20194. View

18.

Israel M, Dunant Y, Manaranche R . The present status of the vesicular hypothesis. Prog Neurobiol. 1979; 13(3):237-75. DOI: 10.1016/0301-0082(79)90017-0. View

19.

Anderson C, Stevens C . Voltage clamp analysis of acetylcholine produced end-plate current fluctuations at frog neuromuscular junction. J Physiol. 1973; 235(3):655-91. PMC: 1350786. DOI: 10.1113/jphysiol.1973.sp010410. View

20.

Zhou F, Hablitz J . Zinc enhances GABAergic transmission in rat neocortical neurons. J Neurophysiol. 1993; 70(3):1264-9. DOI: 10.1152/jn.1993.70.3.1264. View