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Presynaptic calcium channels: specialized control of synaptic neurotransmitter release

Nature Reviews Neuroscience volume 21, pages 213–229 (2020)Cite this article

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Abstract

Chemical synapses are heterogeneous junctions formed between neurons that are specialized for the conversion of electrical impulses into the exocytotic release of neurotransmitters. Voltage-gated Ca2+ channels play a pivotal role in this process as they are the major conduits for the Ca2+ ions that trigger the fusion of neurotransmitter-containing vesicles with the presynaptic membrane. Alterations in the intrinsic function of these channels and their positioning within the active zone can profoundly alter the timing and strength of synaptic output. Advances in optical and electron microscopic imaging, structural biology and molecular techniques have facilitated recent breakthroughs in our understanding of the properties of voltage-gated Ca2+ channels that support their presynaptic functions. Here we examine the nature of these channels, how they are trafficked to and anchored within presynaptic boutons, and the mechanisms that allow them to function optimally in shaping the flow of information through neural circuits.

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Fig. 1: Cav channel nomenclature and properties.
Fig. 2: Synthesis and trafficking of Cav channels.
Fig. 3: Regulation of Cav1 channel inactivation at ribbon synapses.
Fig. 4: Organization and modulation of Cav2 channels in synapses.
Fig. 5: Differential synaptic recruitment of Cav channel regulatory mechanisms.

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Acknowledgements

This work was supported by a Wellcome Trust Investigator award (206279/Z/17/Z) to A.C.D. and US National Institutes of Heath grants NS084190, DC009433 and EY026817 to A.L.

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Authors and Affiliations

  1. Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK

    Annette C. Dolphin

  2. Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, USA

    Amy Lee

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  1. Annette C. Dolphin
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The authors contributed equally to all aspects of the article.

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Nature Reviews Neuroscience thanks D. Lipscombe, T. Takahashi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Auxiliary subunits

Subunits that modify the activity and/or trafficking of the pore-forming subunit.

Alternative splicing

The process in which certain exons are included or excluded to produce multiple different mRNAs from a single gene.

Activation voltages

The membrane potentials at which a channel's open probability increases, which can be quantified in terms of the voltage for half-maximal activation.

Channel pore

The ion conduction pathway of a channel.

Selectivity filter

The part of the channel pore that restricts passage of particular ions, for example for Ca2+ ions within a voltage-gated Ca2+ channel.

Ribbon synapses

Synapses characterized by a synaptic ribbon that is specialized for the transmission of sensory information.

Calmodulin

A multifunctional Ca2+-sensing protein found in all eukaryotic cells.

Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) proteins

Members of a protein complex that mediates the fusion of vesicles with another membrane, for example the plasma membrane.

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Dolphin, A.C., Lee, A. Presynaptic calcium channels: specialized control of synaptic neurotransmitter release. Nat Rev Neurosci 21, 213–229 (2020). https://doi.org/10.1038/s41583-020-0278-2

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