The intracellular Ca ²⁺ sensitivity of transmitter release from neocortical boutons

Synaptotagmin 1 (Syt1) and Syt2 are the main Ca ²⁺ sensors triggering synchronous release in the brain. The Ca ²⁺ -sensitivity of Syt2-triggered release has been studied in detail. However, for Syt1, the dominating isoform in the neocortex, quantitative detail is lacking. We measured the Ca ²⁺ -dependency of Syt1-triggered release at layer 5 pyramidal neuron synapses by laser photolysis of caged Ca ²⁺ . Syt1-triggered release had high Ca ²⁺ affinity and positive cooperativity (EC ₅₀ , 20 μM; Hill coefficient, 3.57). It was steep in a dynamic range between ∼10 and ∼30 μM that was covered by action potential-evoked release. A kinetic model reveals significant differences to models of Syt2-triggered release. Our results suggest that Syt1 optimizes neocortical synapses for high reliability at moderate local Ca ²⁺ elevations and for high plastic controllability.