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Ca2+buffering as a mechanism of short-term synaptic plasticity

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Spatio-temporal compartmentalization allows Ca2+ signals to simultaneously regulate multiple vital cell processes and relies in part on Ca2+ buffers that absorb at least 98% of Ca2+ ions entering the cytoplasm. Computational modeling has played a central role in the understanding of localized Ca2+ signals in neurons and other cell types. Although many models consider only simple, one-to-one Ca2+ buffering stoichiometry, practically all buffers have multiple Ca2+ binding sites which often display cooperative binding (e.g., calretinin [13], calmodulin [4, 5] ). Given the simplest case of two binding sites, cooperativity manifests itself in an order of magnitude difference in the binding and/or unbinding rates of the two consecutive Ca2+ binding steps in the following buffer reaction:

Here we extend recent modeling studies of cooperative buffering [15], and find that it can lead to spatio-temporal Ca2+ signals that cannot be achieved by any combination of non-cooperative buffers, in particular during a sequence of action potentials or synaptic inputs. Namely, Figure 1B shows that cooperative Ca2+ buffering can potentially serve as a mechanism of short-term synaptic depression, in contrast to the case of non-cooperative buffers (Figure 1A), which are believed to underlie short-term synaptic facilitation in certain types of mammalian synapses [6, 7].

Figure 1
figure1

[Ca2+] elevation during a 40 Hz train of 1ms-long Ca2+ pulses at 100nm from the Ca2+ source. A: In the presence of a non-cooperative buffer, Ca2+ transients facilitate due to gradual depletion (saturation) of free buffer [6, 7]. B: In the presence of a cooperative buffer, Ca2+ transients depress as a result of increasing exposure of the high-affinity Ca2+ binding site. Both simulations done in 1D geometry (0.5 μm axonal segment), computed using CalC version 7.2 (http://www.calciumcalculator.org)

We explore this phenomenon in detail, demonstrating the dependence of such buffer-induced short-term synaptic plasticity on all relevant buffering parameters. These results may lead to better understanding of post-synaptic Ca2+ dynamics as well, yielding a deeper insight into synaptic transmission and its dynamic regulation, and may also have relevance for Ca2+-dependent processes in other cells such as endocrine cells, myocytes and immune system cells.

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Acknowledgements

This work was supported in part by NSF grant DMS-0817703.

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Correspondence to Victor Matveev.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Matveev, V. Ca2+buffering as a mechanism of short-term synaptic plasticity. BMC Neurosci 14, P269 (2013) doi:10.1186/1471-2202-14-S1-P269

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Keywords

  • Synaptic Transmission
  • Buffer Reaction
  • Deep Insight
  • Endocrine Cell
  • Cell Process