Figure 2.

Ca²⁺ signaling domains. (A) General Ca²⁺ dynamics: Ca²⁺ enters a presynaptic terminal through a voltage-gated Ca²⁺ channel. Due to rapid diffusion (indicated by red gradient and the arrows) Ca²⁺ forms a steep, short-lived spatio-temporal gradient around the mouth of the open channel. It binds to mobile or fix Ca²⁺-binding proteins (CaBPs); some CaBP are pure buffers, others have an additional Ca²⁺ sensor function. Ultimately Ca²⁺ is cleared from the cytosol via Ca²⁺-ATPases (white circles with arrows) that either pump Ca²⁺ into the extracellular space or sequester it into organelles. (B) In a tight coupling regime a Syt bearing SV is located very close to the site of Ca²⁺ entry (<50 nm). If coupling is tight, at moderate concentrations only a buffer with rapid Ca²⁺ binding kinetics like BAPTA (red) can interfere with Ca²⁺ binding to Syt and prevent release. In a loose coupling regime, on the other hand, the SV is further away from the site of Ca²⁺ entry and also a slow buffer like EGTA (blue) can bind Ca²⁺ before it reaches the release sensor.