突触前末端的电压门控钙通道的激活导致钙的局部增加和含有神经递质的突触小泡的融合。突触前输出是钙通道密度的函数,通道的动态特性,到对接囊泡的距离,以及对接地点的释放概率。我们证明,在秀丽隐杆线虫神经肌肉接头两种不同类型的电压门控钙通道,CaV2和CaV1介导突触小泡的不同池的释放。CaV2通道集中在直径为〜250nm的密集堆积簇,活性区蛋白Neurexin,α-立普林,SYDE,ELKS/CAST,RIM-BP,α-Catulin,MAGI1CaV2通道与引发蛋白UNC-13L共定位,并介导在致密突起的33nm内对接的囊泡的融合。通过ryanodine受体从内部存储中释放钙,可以放大CaV2活性,触发融合高达165nm的密集投影。相比之下,CaV1通道分散在突触静脉曲张中,并与UNC-13S共同定位。CaV1和ryanodine受体仅相隔40nm,CaV1介导的囊泡融合完全依赖于ryanodine受体。不同的突触小泡池,通过不同的钙通道释放,可以用来调整速度,电压依赖性,和神经递质释放的定量含量。
Activation of voltage-gated calcium channels at presynaptic terminals leads to local increases in calcium and the fusion of synaptic vesicles containing neurotransmitter. Presynaptic output is a function of 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 Caenorhabditis elegans neuromuscular junctions two different classes of voltage-gated calcium channels, CaV2 and CaV1, mediate the release of distinct pools of synaptic vesicles. CaV2 channels are concentrated in densely packed clusters ~250 nm in diameter with the active zone proteins Neurexin, α-Liprin, SYDE, ELKS/CAST, RIM-BP, α-Catulin, and MAGI1. CaV2 channels are colocalized with the priming protein UNC-13L and mediate the fusion of vesicles docked within 33 nm of the dense projection. CaV2 activity is amplified by ryanodine receptor release of calcium from internal stores, triggering fusion up to 165 nm from the dense projection. By contrast, CaV1 channels are dispersed in the synaptic varicosity, and are colocalized with UNC-13S. CaV1 and ryanodine receptors are separated by just 40 nm, and vesicle fusion mediated by CaV1 is completely dependent on the ryanodine receptor. Distinct synaptic vesicle pools, released by different calcium channels, could be used to tune the speed, voltage-dependence, and quantal content of neurotransmitter release.