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Presynaptic Ca2+ buffers control the strength of a fast post-tetanic hyperpolarization mediated by the α3 Na+/K+-ATPase

Nature Neuroscience volume 10, pages 196–205 (2007)Cite this article

Abstract

The excitability of CNS presynaptic terminals after a tetanic burst of action potentials is important for synaptic plasticity. The mechanisms that regulate excitability, however, are not well understood. Using direct recordings from the rat calyx of Held terminal, we found that a fast Na+/K+-ATPase (NKA)-mediated post-tetanic hyperpolarization (PTH) controls the probability and precision of subsequent firing. Notably, increasing the concentration of internal Ca2+ buffers or decreasing Ca2+ influx led to larger PTH amplitudes, indicating that an increase in [Ca2+]i regulates PTH via inhibition of NKAs. The characterization for the first time of a presynaptic NKA pump current, combined with immunofluorescence staining, identified the α3-NKA isoform on calyx terminals. Accordingly, the increased ability of the calyx to faithfully fire during a high-frequency train as it matures is paralleled by a larger expression of α3-NKA during development. We propose that this newly discovered Ca2+ dependence of PTH is important in the post-burst excitability of nerve terminals.

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Figure 1: PTH acquires a faster onset and two decay components during developmental maturation.
Figure 2: PTH is mediated mostly by NKA.
Figure 3: PTH decay: Ih mediates the slow decay component of PTH.
Figure 4: Reduced Ca2+ influx increases PTH amplitude.
Figure 5: Intracellular Ca2+ buffering regulates PTH amplitude.
Figure 6: NKA pump currents in a presynaptic terminal.
Figure 7: α-NKA expression during development.
Figure 8: PTH increases calyx action potential latencies and EPSC delays.

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Acknowledgements

We thank E. McCleskey and D. Gadsby for insightful discussions, and J. Adelman, C. Jahr, J. Maylie and L. Trussell for comments on the manuscript. This work was supported by a US National Institute of Deafness and Communication Disorders grant (DC04274, H.v.G.), an American Heart Association postdoctoral grant (J.H.K.) and a US National Institute of Diabetes and Digestive and Kidney Diseases grant (DK067248, M.D.).

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  1. The Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, 97239, Oregon, USA

    Jun Hee Kim & Henrique von Gersdorff

  2. Department of Anesthesiology, University of Arkansas for Medical Sciences, 4301 Weat Markham Street, Little Rock, 72205, Arkansas, USA

    Igor Sizov & Maxim Dobretsov

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  1. Jun Hee Kim
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J.H.K. performed all experiments, J.H.K. and H.v.G. performed data analysis and J.H.K., I.S., M.D. and H.v.G. wrote the paper.

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Correspondence to Henrique von Gersdorff.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

PTH induced by high-frequency trains in the calyx of Held has two kinetic components. (PDF 279 kb)

Supplementary Fig. 2

The fast decay of PTH: mediated by a depolarizing K+current or NKA inactivation. (PDF 149 kb)

Supplementary Fig. 3

AP failures and recovery time course of latencies during PTH. (PDF 188 kb)

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Kim, J., Sizov, I., Dobretsov, M. et al. Presynaptic Ca2+ buffers control the strength of a fast post-tetanic hyperpolarization mediated by the α3 Na+/K+-ATPase. Nat Neurosci 10, 196–205 (2007). https://doi.org/10.1038/nn1839

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