Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USA.
J Physiol. 2011 May 15;589(Pt 10):2497-514. doi: 10.1113/jphysiol.2011.206631. Epub 2011 Mar 21.
Nigral dopamine neurons are transiently activated by high frequency glutamatergic inputs relaying reward-predicting sensory information. The tonic firing pattern of dopamine cells responds to these inputs with a transient burst of spikes that requires NMDA receptors. Here, we show that NMDA receptor activation further excites the cell by recruiting a calcium-activated non-selective cation current (ICAN) capable of generating a plateau potential. Burst firing in vitro is eliminated after blockade of ICAN with flufenamic acid, 9-phenanthrol, or intracellular BAPTA. ICAN is likely to be mediated by a transient receptor potential (TRP) channel, and RT-PCR was used to confirm expression of TRPM2 and TRPM4mRNA in substantia nigra pars compacta.We propose that ICAN is selectively activated during burst firing to boost NMDA currents and allow plateau potentials. This boost mechanism may render DA cells vulnerable to excitotoxicity.
黑质多巴胺神经元会被传递奖励预测感觉信息的高频谷氨酸能传入短暂激活。多巴胺细胞的紧张性放电模式会对这些输入产生短暂的尖峰爆发反应，这需要 NMDA 受体。在这里，我们表明 NMDA 受体的激活通过募集钙激活的非选择性阳离子电流 (ICAN) 进一步兴奋细胞，该电流能够产生平台电位。用氟芬那酸、9-菲咯啉或细胞内 BAPTA 阻断 ICAN 后，体外爆发放电被消除。ICAN 可能由瞬时受体电位 (TRP) 通道介导，RT-PCR 用于确认 TRPM2 和 TRPM4mRNA 在黑质致密部中的表达。我们提出，ICAN 在爆发放电期间被选择性激活以增强 NMDA 电流并允许产生平台电位。这种增强机制可能使 DA 细胞易受兴奋性毒性影响。
