Fortin Gabriel D, Desrosiers Catherine C, Yamaguchi Nobuharu, Trudeau Louis-Eric
Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montreal, Quebec.
J Neurochem. 2006 Mar;96(6):1740-9. doi: 10.1111/j.1471-4159.2006.03699.x.
Dopaminergic neurons have the capacity to release dopamine not only from their axon terminals, but also from their somatodendritic compartment. The actual mechanism of somatodendritic dopamine release has remained controversial. Here we established for the first time a rat primary neuron culture model to investigate this phenomenon and use it to study the mechanism under conditions of non-stimulated spontaneous firing (1-2 Hz). We found that we can selectively measure somatodendritic dopamine release by lowering extracellular calcium to 0.5 mm, thus confirming the previously established differential calcium sensitivity of somatodendritic and terminal release. Dopamine release measured under these conditions was dependent on firing activity and independent of reverse transport through the plasma membrane. We found that treatment with botulinum neurotoxins A and B strongly reduced somatodendritic dopamine release, thus demonstrating the requirement for SNARE proteins SNAP-25 and synaptobrevin. Our work is the first to provide such direct and unambiguous evidence for the involvement of an exocytotic mechanism in basal spontaneous somatodendritic dopamine release.
多巴胺能神经元不仅能够从其轴突终末释放多巴胺，还能从其胞体树突部分释放多巴胺。胞体树突多巴胺释放的实际机制一直存在争议。在此，我们首次建立了大鼠原代神经元培养模型来研究这一现象，并利用该模型在非刺激自发放电（1 - 2赫兹）条件下研究其机制。我们发现，通过将细胞外钙浓度降至0.5毫摩尔，可以选择性地测量胞体树突多巴胺释放，从而证实了先前确立的胞体树突释放和终末释放对钙敏感性的差异。在这些条件下测得的多巴胺释放依赖于放电活动，且与通过质膜的逆向转运无关。我们发现，用肉毒杆菌神经毒素A和B处理可强烈减少胞体树突多巴胺释放，从而证明了对SNARE蛋白SNAP - 25和突触小泡蛋白的需求。我们的工作首次为胞吐机制参与基础自发胞体树突多巴胺释放提供了如此直接和明确的证据。
