Why does a small change in calcium entry change transmitter release so much? · Grey Matter

A vesicle fuses only when several calcium ions are bound to its sensor, synaptotagmin, so release grows roughly as release∝[Ca2+]4\text{release} \propto [\text{Ca}^{2+}]^{4}release∝[Ca2+]4, a relation first measured by Dodge and Rahamimoff in 1967.

Why does a small change in calcium entry change transmitter release so much?

A vesicle fuses only when several calcium ions are bound to its sensor, synaptotagmin, so release grows roughly as release∝[Ca2+]4\text{release} \propto [\text{Ca}^{2+}]^{4}release∝[Ca2+]4, a relation first measured by Dodge and Rahamimoff in 1967. With that exponent, calcium entry cut by a fifth leaves 0.84≈0.410.8^{4} \approx 0.410.84≈0.41 of the release. The steepness makes calcium channels a powerful control point: presynaptic receptors for GABA, endocannabinoids or adenosine need only trim calcium entry slightly to silence a synapse. It also makes residual calcium from an earlier spike matter, which underlies facilitation.