ETHANOL ACTIVATION TONICALLY ACTIVATE GLYCINE RECEPTORS

酒精引起的许多抑制作用被认为源于中枢神经系统抑制性神经传递的增强，特别是GABAA和甘氨酸受体功能的增强。甘氨酸受体调节剂包括各种各样的化合物，包括酒精和吸入剂等滥用药物，以及临床使用的挥发性麻醉剂和戊巴比妥等药物。虽然已知这些调节剂增强甘氨酸受体介导的电流，但更具体的分子机制尚不清楚。通过研究一种甘氨酸受体，它在没有神经递质的情况下激活，但仍能被酒精调节，这可能会发现对激活机制的新见解。对配体门控离子通道受体机制的更好理解可能会导致治疗药物，如酒精中毒治疗方案和副作用更小的麻醉剂。所提出的工作不仅可以揭示乙醇和其他受体调节剂的分子机制，而且还可以更全面地了解基本的受体/通道过程。

Many of the depressant effects caused by alcohol are believed to stem from an enhancement of inhibitory neurotransmission in the central nervous system, specifically the enhancement of GABAA and glycine receptor function. Glycine receptor modulators include a wide variety of chemical compounds including drugs of abuse like alcohol and inhalants, as well as clinically used drugs like volatile anesthetics and pentobarbital. While it is known that these modulators enhance glycine receptor-mediated currents, more specific molecular mechanisms have eluded us. By studying a glycine receptor that activates in the absence of neurotransmitter but retains its ability to be modulated by alcohol, new insights into activation mechanisms could be discovered. A better understanding of ligand-gated ion channel receptor mechanisms could lead to therapeutic agents such as alcoholism treatment regimens and anesthetics with fewer side effects. The work proposed may not only shed insights into the molecular mechanisms of ethanol and other receptor modulators, but also provide a fuller understanding of basic receptor/channel processes.