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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Dopamine transporters depolarize neurons by a channel mechanism.
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Dopamine transporters depolarize neurons by a channel mechanism.

机译：多巴胺转运蛋白通过通道机制使神经元去极化。

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Neurotransmitter transporters generate larger currents than expected if one assumes fixed stoichiometry models. It remains controversial, however, whether these depolarizing currents arise from high density and rapid turnover rates of a classical transporter, or whether transporters exhibit bona fide channel behavior. Although heterologously expressed transporters show single-channel behavior and noise analysis in native cells strongly suggests channel behavior, no directly observed single-channel events associated with transporters have been reported thus far in native cells. We describe single-channel events arising directly from the Caenorhabditis elegans dopamine transporter (DAT-1) as evidenced by DA-induced channel activity blocked by a high-affinity DAT-1 inhibitor, increased channel activity in neurons that overexpress DAT-1, and loss of channels in dat-1 knockout neurons. Our data indicate that authentic transporter channels underlie depolarizing whole-cell currents. Thus, DA transporters not only transport DA but also exhibit a channel mode of conduction that directly modulates membrane potential and neuronal function.
机译：如果假定固定的化学计量模型，神经递质转运蛋白产生的电流会比预期的大。但是，这些去极化电流是由传统转运蛋白的高密度和快速周转率引起的，还是由转运蛋白表现出真实的通道行为，仍然存在争议。尽管异源表达的转运蛋白显示出单通道行为，并且在天然细胞中的噪声分析强烈暗示了通道行为，但迄今为止，尚未报道天然细胞中与转运蛋白相关的直接观察到的单通道事件。我们描述了直接由秀丽隐杆线虫多巴胺转运蛋白（DAT-1）引起的单通道事件，DA诱导的通道活性被高亲和力的DAT-1抑制剂阻滞，在过表达DAT-1的神经元中通道活性增加，和dat-1基因敲除神经元通道丢失。我们的数据表明，真实的转运通道是全细胞电流去极化的基础。因此，DA转运蛋白不仅转运DA，而且还表现出直接调节膜电位和神经元功能的传导通道模式。

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