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 [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].