CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles

Abstract

Activation of voltage-gated calcium channels at synapses leads to local increases in calcium and the fusion of synaptic vesicles. However, presynaptic output will be determined by the density of calcium channels, the dynamic properties of the channel, the distance to docked vesicles, and the release probability at the docking site. We demonstrate that at C. elegans neuromuscular junctions, CaV2, and CaV1 mediate the release of two distinct pools of synaptic vesicles. Superresolution microscopy demonstrates that CaV2 channels are concentrated in densely packed clusters ~300 nm in diameter with active zone proteins Neurexin, α-Liprin, SYDE, ELKS, RIMB, α Catulin, and MAGI. The CaV2 channels mediate the fusion of vesicles docked within 100 nm of the dense projection and is colocalized with to the synaptic vesicle priming protein UNC 13L. By contrast, CaV1 channels are dispersed in the synaptic varicosity and are coupled to internal calcium stores via the ryanodine receptor. The CaV1 and ryanodine receptor mediate the fusion of vesicles docked broadly in the synaptic varicosity and are colocalized with the vesicle priming protein UNC-13S. These distinct synaptic vesicle pools, released by different calcium channels, could be used to tune the speed, voltage-dependence, and quantal content of neurotransmitter release.