An integrated model for calcium dynamics during synaptic transmission

We present an integrated model for calcium dynamics at presynaptic terminals during synaptic transmission, incorporating regulatory mechanisms known to regulate vesicle release. One of the novel features of our model is that we have made a distinction between processes occurring on the membrane or not. Thus, we have been able to address how geometric characteristics of the presynaptic terminal affect the dynamics of calcium in the presynaptic terminal. Buffering mechanisms and depletion of extracellular calcium are defined in the cytoplasm and synaptic cleft whereas calcium-induced-calcium-release mechanisms from the ER is considered a membrane-delimited process. We propose a simple kinetic scheme for a membrane-delimited modulation of voltage-gated calcium channels on the presynaptic face that is triggered by G-protein activation. We have studied each process with respect to characteristic space and time scales for vesicle release so that we can address their relative influence on neurotransmission modulation. The analysis of our model suggests the existence of a feedback loop mechanism that down- or up-regulate calcium influx during stimulation at presynaptic terminals depending on the precise interactions among all processes considered in our model. Two-dimensional simulations were implemented so that we could address how all processes previously described interact with each other and how these interactions affect the overall dynamics of calcium and hence transmitter release.