Lovinger D M
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA.
Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep;356(3):267-82. doi: 10.1007/pl00005051.
The neurotransmitter-gated ion channels form a superfamily of neurotransmitter receptors specialized for recognizing transmitters and rapidly gating ion channels that are contained within the same holoprotein complex. A large body of research indicates that alcohols alter the function of this class of receptor at concentrations relevant to the intoxicating and anesthetic effects of the alcohols. In addition, studies have implicated several types of neurotransmitter-gated channels in intoxicating and anesthetic alcohol actions. All of the neurotransmitter-gated ion channels contain conserved features such as N-terminal ligand binding domains, hydrophobic membrane spanning domains and charged pore-lining domains. However, at least two, and possibly three families of receptors have been identified within the superfamily, including the nicotinic ACh-like receptors, the ionotropic glutamate receptors and the ATP-gated ion channels. This review will begin with a brief overview of the structural features of the different receptors, with an emphasis on comparing and contrasting features of the different families of neurotransmitter-gated channels. The emphasis will be mostly on the nicotinic-like receptors and the iGluRs, since more is known about these receptors than about other types of ligand-activated cation channels. The remainder of the review focuses on the latest studies aimed at determining the mechanism of alcohol actions on this superfamily of receptor-channels as well as the relationship between the molecular structure of these channels and the effects of alcohols on channel function. In addition, emerging directions for future study of these effects of alcohols and possible regions of the protein that may be altered during alcohol exposure are discussed.
神经递质门控离子通道构成了一个神经递质受体超家族，专门用于识别递质并快速控制包含在同一完整蛋白复合物中的离子通道。大量研究表明，酒精在与酒精的中毒和麻醉作用相关的浓度下会改变这类受体的功能。此外，研究表明几种类型的神经递质门控通道与酒精的中毒和麻醉作用有关。所有神经递质门控离子通道都具有保守特征，如N端配体结合结构域、疏水跨膜结构域和带电荷的孔衬结构域。然而，在这个超家族中已鉴定出至少两个，可能是三个受体家族，包括烟碱样乙酰胆碱受体、离子型谷氨酸受体和ATP门控离子通道。本综述将首先简要概述不同受体的结构特征，重点是比较和对比不同神经递质门控通道家族的特征。重点将主要放在烟碱样受体和离子型谷氨酸受体上，因为关于这些受体的了解比对其他类型的配体激活阳离子通道的了解更多。综述的其余部分重点关注旨在确定酒精对这个受体通道超家族作用机制的最新研究，以及这些通道的分子结构与酒精对通道功能影响之间的关系。此外，还讨论了酒精这些作用未来研究的新方向以及酒精暴露期间可能发生改变的蛋白质区域。
