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Tracking presynaptic Ca2+ dynamics during neurotransmitter release with Ca2+-activated K+ channels

Nature Neuroscience volume 3, pages 566–571 (2000)Cite this article

Abstract

Neurotransmitter release during action potentials is thought to require transient, localized [Ca2+]i as high as hundreds of micromolar near presynaptic release sites. Most experimental attempts to characterize the magnitude and time course of these Ca2+ domains involve optical methods that sample large volumes, require washout of endogenous buffers and often affect Ca2+ kinetics and transmitter release. Endogenous calcium-activated potassium (KCa) channels colocalize with presynaptic Ca2+ channels in Xenopus nerve–muscle cultures. We used these channels to quantify the rapid, dynamic changes in [Ca2+]i at active zones during synaptic activity. Confirming Ca2+-domain predictions, these KCa channels revealed [Ca2+]i over 100 μM during synaptic activity and much faster buildup and decay of Ca2+ domains than shown using other techniques.

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Figure 1: IK-Ca and EPSCs in response to different amounts of Ca2+ entry obtained by truncation of a calcium tail current (ICa).
Figure 2: Peak evokable IK-Ca and neurotransmitter release as a function of Ca2+ entry during a calcium tail current (from experiment in Fig. 1).
Figure 3: Calibration of average [Ca2+]AZ near KCa channels during Ca2+ transients.
Figure 4: ICa, IK-Ca, calculated [Ca2+] and EPSC magnitude as a function of time during a simulated action potential.
Figure 5: Ca2+ concentration changes and transmitter release at different rates of Ca2+ entry.

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Acknowledgements

This work was supported by NIH, NSF and the Spinal Cord Research Foundation. We thank M. Harvey for help with the experiments, A. Peskoff for expertise in Ca2+ domain modeling and E. Stefani, F. Bezanilla, D. DiGregorio and B. Edmonds for comments on the manuscript.

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Authors and Affiliations

  1. Department of Physiology and Jerry Lewis Neuromuscular Research Center, UCLA School of Medicine, Los Angeles, 90095, California, USA

    Bruce Yazejian, Xiao-Ping Sun & Alan D. Grinnell

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  1. Bruce Yazejian
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  3. Alan D. Grinnell
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Correspondence to Alan D. Grinnell.

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Yazejian, B., Sun, XP. & Grinnell, A. Tracking presynaptic Ca2+ dynamics during neurotransmitter release with Ca2+-activated K+ channels. Nat Neurosci 3, 566–571 (2000). https://doi.org/10.1038/75737

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