Organization and function of transmitter release sites at the neuromuscular junction

Authors

  • Stephen D. Meriney,

    1. Department of Neuroscience, Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA
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  • Markus Dittrich

    1. Department of Neuroscience, Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA
    2. National Resource for Biomedical Supercomputing, Pittsburgh Supercomputing Center, Pittsburgh, PA 15213, USA
    3. Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA
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  • This review was presented at The Journal of Physiology Symposium entitled ‘Size matters: formation and function of GIANT synapses’, which took place at the Annual meeting of the Society for Neuroscience, New Orleans, LA, USA, on 12 October 2012. It was commissioned by the Editorial Board and reflects the views of the authors.

S. D. Meriney: Department of Neuroscience, University of Pittsburgh, A210 Langley Hall, Pittsburgh, PA 15260, USA. Email: meriney@pitt.edu

Abstract

Abstract  The neuromuscular junction is known as a strong and reliable synapse. It is strong because it releases an excess of chemical transmitter, beyond what is required to bring the postsynaptic muscle cell to threshold. Because the synapse can sustain suprathreshold muscle activation during short trains of action potentials, it is also reliable. The presynaptic mechanisms that lead to reliability during short trains of activity have only recently been elucidated. It appears that there are relatively few calcium channels in individual active zones, that channels open with a low probability during action potential stimulation and that even if channels open the resulting calcium flux only rarely triggers vesicle fusion. Thus, each synaptic vesicle may only associate with a small number of calcium channels, forming an unreliable single vesicle release site. Strength and reliability of the neuromuscular junction emerge as a result of its assembly from thousands of these unreliable single vesicle release sites. Hence, these synapses are strong while at the same time only releasing a small subset of available docked vesicles during each action potential, thus conserving transmitter release resources. This prevents significant depression during short trains of action potential activity and confers reliability.

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