Liu J C, DeFazio R A, Espinosa-Jeffrey A, Cepeda C, de Vellis J, Levine M S
Mental Retardation Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
J Neurosci Res. 2004 May 1;76(3):315-22. doi: 10.1002/jnr.20079.
In the striatum, dopamine (DA) exerts a major modulatory influence on voltage- and ligand-gated currents. Previously we have shown that DA modulates glutamatergic neurotransmission and that the direction of this modulation depends on, among other factors, the glutamate and DA receptor subtypes activated. These effects also involve DA-induced alterations in voltage-gated Ca(2+) currents. In the present experiments, the effects of Ca(2+) channel blockers on DA and D1 receptor-dependent potentiation of N-methyl-D-aspartate (NMDA) responses were examined in vitro in striatal slices using current clamp recording techniques. DA or D1 receptor agonists consistently enhanced NMDA responses. Cadmium and the more selective L-type Ca(2+) channel antagonists nifedipine and methoxyverapamil reduced the potentiation of NMDA responses by DA or D1 receptor activation. Furthermore, studies using Ca(2+) imaging with Fluo-3 in cultured cortical or dissociated striatal neurons demonstrated that DA and D1 agonists increased intracellular Ca(2+) transients induced by NMDA. These as well as previous findings indicate that in striatal neurons at least two mechanisms contribute to the enhancement of NMDA responses by DA receptor activation, facilitation of voltage-gated Ca(2+) currents and D1 receptor activation of the cAMP-protein kinase A cascade. The existence of multiple mechanisms leading to a similar outcome allows a certain degree of redundancy in the consequences of DA modulation.
在纹状体中，多巴胺（DA）对电压门控电流和配体门控电流发挥着主要的调节作用。此前我们已经表明，DA可调节谷氨酸能神经传递，并且这种调节的方向除其他因素外，还取决于激活的谷氨酸和DA受体亚型。这些效应还涉及DA诱导的电压门控Ca(2+)电流的改变。在本实验中，使用电流钳记录技术在体外纹状体切片中研究了Ca(2+)通道阻滞剂对DA和D1受体依赖性N-甲基-D-天冬氨酸（NMDA）反应增强作用的影响。DA或D1受体激动剂持续增强NMDA反应。镉以及更具选择性的L型Ca(2+)通道拮抗剂硝苯地平和甲氧基维拉帕米降低了DA或D1受体激活对NMDA反应的增强作用。此外，在培养的皮质神经元或解离的纹状体神经元中使用Fluo-3进行Ca(2+)成像的研究表明，DA和D1激动剂增加了由NMDA诱导的细胞内Ca(2+)瞬变。这些以及先前的研究结果表明，在纹状体神经元中，至少有两种机制导致DA受体激活增强NMDA反应，即促进电压门控Ca(2+)电流和cAMP-蛋白激酶A级联的D1受体激活。导致相似结果的多种机制的存在使得DA调节的后果具有一定程度的冗余性。
