Skip to main content


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

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

[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 (

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.


  1. 1.

    Saftenku EE: Effects of Calretinin on Ca2+ Signals in Cerebellar Granule Cells: Implications of Cooperative Ca2+ Binding. Cerebellum. 2011, 11 (1): 102-120.

  2. 2.

    Schwaller B: The continuing disappearance of "pure" Ca2+ buffers. Cell Mol Life Sci. 2009, 66 (2): 275-300. 10.1007/s00018-008-8564-6.

  3. 3.

    Faas GC, Schwaller B, Vergara JL, Mody I: Resolving the fast kinetics of cooperative binding: Ca2+ buffering by calretinin. PLoS Biol. 2007, 5 (11): e311-10.1371/journal.pbio.0050311.

  4. 4.

    Faas GC, Raghavachari S, Lisman JE, Mody I: Calmodulin as a direct detector of Ca2+ signals. Nat Neurosci. 2011, 14 (3): 301-304. 10.1038/nn.2746.

  5. 5.

    Kubota Y, Waxham MN: Lobe specific Ca2+-calmodulin nano-domain in neuronal spines: a single molecule level analysis. PLoS Comput Biol. 2010, 6 (11): e1000987-10.1371/journal.pcbi.1000987.

  6. 6.

    Burnashev N, Rozov A: Presynaptic Ca2+ dynamics, Ca2+ buffers and synaptic efficacy. Cell Calcium. 2005, 37 (5): 489-495. 10.1016/j.ceca.2005.01.003.

  7. 7.

    Matveev V, Zucker RS, Sherman A: Facilitation through buffer saturation: constraints on endogenous buffering properties. Biophys J. 1993, 86: 2691-2701.

Download references


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

Author information

Correspondence to Victor Matveev.

Rights and permissions

Reprints and Permissions

About this article


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