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Light at the end of the channel: optical manipulation of intrinsic neuronal excitability with chemical photoswitches

机译:通道末端的光:化学光开关对内在神经元兴奋性的光学操纵

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摘要

Ion channels are transmembrane proteins that control the movement of ions across the cell membrane. They are the molecular machines that make neurons excitable by enabling the initiation and propagation of action potentials (APs). Rapid signaling within and between neurons requires complex molecular processes that couple the sensing of membrane voltage or neurotransmitter release to the fast opening and closing of the ion channel gate. Malfunction of an ion channel's sensing or gating module can have disastrous pathological consequences. However, linking molecular changes to the modulation of neural circuits and ultimately to a physiological or pathological state is not a straightforward task. It requires precise and sophisticated methods of controlling the function of ion channels in their native environment. To address this issue we have developed new photochemical tools that enable the remote control of neuronal ion channels with light. Due to its optical nature, our approach permits the manipulation of the nervous system with high spatial, temporal and molecular precision that will help us understand the link between ion channel function and physiology. In addition, this strategy may also be used in the clinic for the direct treatment of some neuronal disorders.
机译:离子通道是跨膜蛋白,可控制离子在细胞膜上的移动。它们是通过激活和传播动作电位(AP)使神经元兴奋的分子机器。神经元内部和神经元之间的快速信号传递需要复杂的分子过程,这些过程将膜电压或神经递质释放的感应与离子通道门的快速打开和关闭相结合。离子通道的感应或门控模块故障可能会造成灾难性的病理后果。然而,将分子变化与神经回路的调节并最终与生理或病理状态联系起来并不是一件容易的事。它需要精确和复杂的方法来控制其自然环境中离子通​​道的功能。为了解决这个问题,我们开发了新的光化学工具,可以用光遥控神经元离子通道。由于其光学性质,我们的方法允许以较高的空间,时间和分子精度来操纵神经系统,这将有助于我们了解离子通道功能与生理之间的联系。另外,该策略也可以在临床中用于直接治疗某些神经元疾病。

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