Dopamine-mediated volume transmission in midbrain is regulated by distinct extracellular geometry and uptake
Dopamine-mediated volume transmission in midbrain is regulated by distinct extracellular geometry and uptake
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DOI：
10.1152/jn.2001.85.4.1761
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发表时间：
2001-04-01
影响因子：
2.5
通讯作者：
Rice, ME
中科院分区：
文献类型：
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作者：
Cragg, SJ;Nicholson, C;Rice, ME
中脑多巴胺(DA)的躯体树突释放至少部分是非突触的；此外，中脑DA受体主要是突触外的。因此，躯体树突状细胞DA介导容量传递，其疗效受局部细胞外微环境的扩散和摄取特性调节。在这里，我们定量地评估了豚鼠脑片中黑质致密部(SNC)和网状结构(SNR)、腹侧被盖区(VTA)和大脑皮质的扩散和摄取。用点源扩散结合离子选择性微电极和碳纤维微电极测定了四甲基铵(TMA(+))和DA的扩散、胞外体积分数(α)和弯曲度(Lambda)以及线性摄取(k‘)的几何参数。TMA(+)-弥散测量显示SNC、SNR和VTA的α值高达30%，明显高于皮质的22%。TMA(+)的lambda和k‘值在不同地区相似。点源DA扩散曲线与线性吸收符合较好，SNR和VTA DA的k‘值(0.08-0.09 S(-1))显著高于SNR(0.006 S(-1))，后者DA过程较稀疏。GBR-12909抑制多巴胺摄取使黑质神经元的k‘下降幅度大于室旁核。此外，去甲肾上腺素转运抑制剂地塞帕明在这两个区域的DA摄取略有减少，尽管这只在VTA有统计学意义。我们使用这些数据来模拟DA在中脑的影响半径。从20个囊泡的点源模拟释放产生足以激活受体的DA浓度，最远20微米，这个距离的DA半衰期为几百毫秒。最重要的是，这个模型表明，扩散而不是摄取是中脑DA时间进程的最重要决定因素，这与以摄取为主的纹状体形成了鲜明的对比。这里讨论的问题，虽然特定于中脑中的DA，但说明了与所有细胞外交流相关的基本生物物理性质。
Somatodendritic release of dopamine (DA) in midbrain is, at least in part, nonsynaptic; moreover, midbrain DA receptors are predominantly extrasynaptic. Thus somatodendritic DA mediates volume transmission, with an efficacy regulated by the diffusion and uptake characteristics of the local extracellular microenvironment. Here, we quantitatively evaluated diffusion and uptake in substantia nigra pars compacta (SNc) and reticulata (SNr), ventral tegmental area (VTA), and cerebral cortex in guinea pig brain slices. The geometric parameters that govern diffusion, extracellular volume fraction (alpha) and tortuosity (lambda), together with linear uptake (k'), were determined for tetramethylammonium (TMA(+)), and for DA, using point-source diffusion combined with ion-selective and carbon-fiber microelectrodes. TMA(+)-diffusion measurements revealed a large alpha of 30% in SNc, SNr, and VTA, which was significantly higher than the 22% in cortex. Values for lambda and k' for TMA(+) were similar among regions. Point-source DA-diffusion curves fitted theory well with linear uptake, with significantly higher values of k' for DA in SNc and VTA (0.08-0.09 s(-1)) than in SNr (0.006 s(-1)), where DA processes are sparser. Inhibition of DA uptake by GBR-12909 caused a greater decrease in k' in SNc than in VTA. In addition, DA uptake was slightly decreased by the norepinephrine transport inhibitor, desipramine in both regions, although this was statistically significant only in VTA. We used these data to model the radius of influence of DA in midbrain. Simulated release from a 20-vesicle point source produced DA concentrations sufficient for receptor activation up to 20 mum away with a DA half-life at this distance of several hundred milliseconds. Most importantly, this model showed that diffusion rather than uptake was the most important determinant of DA time course in midbrain, which contrasts strikingly with the striatum where uptake dominates. The issues considered here, while specific for DA in midbrain, illustrate fundamental biophysical properties relevant for all extracellular communication.