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: 542/3/779    most recent 2002.020222v1 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 Congar, P. Articles by Trudeau, L.-E. Search for Related Content PubMed PubMed Citation Articles by Congar, P. Articles by Trudeau, L.-E.

Perturbation of synaptic vesicle delivery during neurotransmitter release triggered independently of calcium influx

Patrice Congar and Louis-Eric Trudeau

Although much evidence suggests that calcium (Ca²⁺) usually triggers synaptic vesicle exocytosis and neurotransmitter release, the role of Ca²⁺ in vesicle endocytosis and in the delivery of fusion-competent vesicles (i.e. mobilisation and/or priming) in nerve terminals remains unclear. To address this issue, we have studied synaptic vesicle dynamics in cultured rat neurones under conditions where neurotransmitter release is triggered independently of Ca²⁺ using the secretagogue Ruthenium Red (RR). Using a prolonged stimulation protocol, we find that RR causes a rapid increase in neurotransmitter release followed by a gradually decrementing response. In contrast, when release is triggered by moderate membrane depolarisation caused by saline containing 18 mM K⁺, release is sustained. These observations suggest that when release is triggered independently of a rise in Ca²⁺, endocytosis or vesicle mobilisation/priming are perturbed. Using FM2-10, a fluorescent indicator of synaptic vesicle cycling, we find that neurotransmitter release triggered by RR is accompanied by both uptake and release of this dye, thereby suggesting that vesicle endocytosis is not blocked. To evaluate whether synaptic vesicle mobilisation/priming is perturbed in the absence of a rise in Ca²⁺, we compared the kinetics of FM2-10 loss during prolonged stimulation. While 18 mM K⁺ induced gradual and continuous dye loss, RR only induced substantial dye loss during the first minute of stimulation. In the presence of low concentrations of the Ca²⁺ ionophore ionomycin, release caused by RR was prolonged. Taken together, these results provide evidence suggesting that, although a rise in intraterminal Ca²⁺ is not required for endocytosis, it is essential for the continuous delivery of fusion-competent vesicles and to maintain neurotransmitter release during prolonged stimulation.

This article has been cited by other articles:

				A. I. Ivanov and R. L. Calabrese Graded Inhibitory Synaptic Transmission Between Leech Interneurons: Assessing the Roles of Two Kinetically Distinct Low-Threshold Ca Currents J Neurophysiol, July 1, 2006; 96(1): 218 - 234. [Abstract] [Full Text] [PDF]

				D.-P. Li, S.-R. Chen, and H.-L. Pan VR1 Receptor Activation Induces Glutamate Release and Postsynaptic Firing in the Paraventricular Nucleus J Neurophysiol, September 1, 2004; 92(3): 1807 - 1816. [Abstract] [Full Text] [PDF]

				S. O. Rizzoli and W. J. Betz Effects of 2-(4-Morpholinyl)-8-Phenyl-4H-1-Benzopyran-4-One on Synaptic Vesicle Cycling at the Frog Neuromuscular Junction J. Neurosci., December 15, 2002; 22(24): 10680 - 10689. [Abstract] [Full Text] [PDF]