SNARE Zippering & Fusion Pore Dynamics

Presynaptic Trigger

Ca²⁺ influx peak 20 µM

Synaptotagmin Ca²⁺ affinity (K_d) 15 µM

Docked SNARE complexes 4

Fusion State

Resting — docked

Zippering

[Ca²⁺] local

0.05 µM

Fusion pore r

0 nm*

NT released

How it works

A synaptic vesicle is held to the plasma membrane by a partially-assembled SNARE complex (synaptobrevin on the vesicle + syntaxin/SNAP-25 on the membrane). An action potential opens voltage-gated Ca²⁺ channels; the resulting local Ca²⁺ domain binds the C2 domains of synaptotagmin-1, the calcium sensor, which releases the clamp on the SNAREs and lets them "zipper" the rest of the way, pulling the two membranes together.

Synaptotagmin binds Ca²⁺ cooperatively — the zippering rate follows a steep Hill relationship:

rate(Ca) = k_max · [Ca]^n / (K_d^n + [Ca]^n),   n ≈ 5

[Ca](t) = Ca_peak · e^(−t/τ)   after each action potential

The steep exponent (n≈5, from five Ca²⁺-binding sites across synaptotagmin's C2A/C2B domains) is why release is an almost all-or-nothing switch a few hundred microseconds after Ca²⁺ enters — small changes in local [Ca²⁺] produce large changes in release probability.

Trigger Action Potential — opens Ca²⁺ channels; watch the blue ions fall onto the docking site and the zippering bar climb.
Ca²⁺ influx peak / K_d sliders — set the driving force and the sensor's affinity; a lower K_d or higher peak reaches full zippering faster.
Docked SNARE complexes — more zippers engaged raises the release probability once triggered (mirrors the readily-releasable pool size).
Full Fusion vs Kiss-and-Run — once the pore nucleates it either dilates fully, collapsing the vesicle into the membrane, or reseals after a brief transient opening, recycling the vesicle intact — both are observed at real synapses.

*Pore radius is shown in simulation units, not literal nanometres — real fusion pores nucleate near ~1 nm and dilate to tens of nm within milliseconds.

Ca²⁺ ion Neurotransmitter Zippered SNARE Unzipped SNARE

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