Figure 8.

The spatial profile of Ca²⁺ underneath the synaptic ribbon. A separate set of simulations was created to describe the spatial extent of local Ca²⁺ microdomains and the influence of the ribbon. A 30 × 30 grid of 10 nm boxes were used to monitor free Ca²⁺ concentration at the presynaptic membrane surface over time while different numbers of channels were opened. To facilitate the grid design, the ribbon was considered a sphere with a flat cap removed to maintain a flat contact area with the presynaptic membrane. Vesicle outlines are depicted as circles within the grid. Shown are free Ca²⁺ concentrations averaged over 1 ms beginning 5 ms after channel opening. In 2 mm EGTA Ca²⁺ buffering conditions (left column), a single open channel (i = −0.54 pA, as expected at V_m = −70 mV) resulted in widespread, large free Ca²⁺ nanodomains. The presence of the ribbon as a diffusion barrier and restrictor of space led to an enhancement in Ca²⁺ concentration of tens of micromolar for hundreds of square nanometers. A comparable peak Ca²⁺ concentration was possible in 10 mm BAPTA buffering conditions (right column) by opening six channels (i = −0.5 pA, as expected at V_m = −60 mV). Although the spatial spread of free Ca²⁺ under 10 mm BAPTA conditions was restricted relative to 2 mm EGTA conditions, the presence of the ribbon as a diffusion barrier remained capable of enhancing Ca²⁺ concentration.