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Ca2+buffering as a mechanism of short-term synaptic plasticity
BMC Neurosciencevolume 14, Article number: P269 (2013)
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 [1–3], 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 [1–5], 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].
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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This work was supported in part by NSF grant DMS-0817703.