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Coactivation of multiple tightly coupled calcium channels triggers spontaneous release of GABA

Nature Neuroscience volume 15, pages 1195–1197 (2012)Cite this article

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Abstract

Voltage-activated Ca2+ channels (VACCs) mediate Ca2+ influx to trigger action potential–evoked neurotransmitter release, but the mechanism by which Ca2+ regulates spontaneous transmission is unclear. We found that VACCs are the major physiological triggers for spontaneous release at mouse neocortical inhibitory synapses. Moreover, despite the absence of a synchronizing action potential, we found that spontaneous fusion of a GABA-containing vesicle required the activation of multiple tightly coupled VACCs of variable type.

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Figure 1: VACCs mediate Ca2+-dependent increases in mIPSC frequency.
Figure 2: Pharmacological dissection of the identity of VACCs mediating spontaneous GABA release.
Figure 3: VACC-vesicle coupling is attenuated by BAPTA-AM, but not by EGTA-AM.

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Acknowledgements

We thank M. Andresen and K. Khodakhah for helpful comments. The work was supported by the US National Institutes of Health (DA027110 and GM097433) and OCTRI. C.W. and N.P.V. were supported by a grant from the National Heart, Lung, and Blood Institute (T32HL033808).

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Author notes

  1. Nicholas P Vyleta

    Present address: Present address: Institute of Science and Technology, Klosterneuburg, Austria.,

  2. Courtney Williams and Wenyan Chen: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon, USA

    Courtney Williams, Wenyan Chen, Chia-Hsueh Lee, Daniel Yaeger, Nicholas P Vyleta & Stephen M Smith

Authors
  1. Courtney Williams
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  2. Wenyan Chen
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  3. Chia-Hsueh Lee
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  6. Stephen M Smith
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Contributions

C.W. conducted the calcium chelation, specific toxin block of mIPSC and VACC currents, and VACC gating experiments, and helped write the manuscript. W.C. conducted the calcium chelation, Cd2+ and specific toxin block of mIPSC and VACC currents, and hyperpolarization experiments. C.-H.L. conducted the calcium concentration effect experiments. D.Y. conducted the Cd2+ block of mIPSC and hyperpolarization experiments. N.P.V. provided cell cultures and helped write the manuscript. S.M.S. designed the experiments, analyzed the data and wrote the manuscript.

Corresponding author

Correspondence to Stephen M Smith.

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The authors declare no competing financial interests.

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Williams, C., Chen, W., Lee, CH. et al. Coactivation of multiple tightly coupled calcium channels triggers spontaneous release of GABA. Nat Neurosci 15, 1195–1197 (2012). https://doi.org/10.1038/nn.3162

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