Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels

致电离效应 神经科学 谷氨酸受体 生物 离子通道 受体 分子药理学 红藻氨酸受体 分子神经科学 计算生物学 遗传学 AMPA受体
作者
Kasper B. Hansen,Lonnie P. Wollmuth,Derek Bowie,Hiro Furukawa,Frank S. Menniti,Alexander I. Sobolevsky,Geoffrey T. Swanson,Sharon A. Swanger,Ingo H. Greger,Terunaga Nakagawa,Chris J. McBain,Vasanthi Jayaraman,Chian-Ming Low,Mark L. Dell’Acqua,Jeffrey S. Diamond,Chad R. Camp,Riley E. Perszyk,Hongjie Yuan,Stephen F. Traynelis
出处
期刊:Pharmacological Reviews [American Society for Pharmacology & Experimental Therapeutics]
卷期号:73 (4): 1469-1658 被引量:206
标识
DOI:10.1124/pharmrev.120.000131
摘要

Many physiologic effects of l-glutamate, the major excitatory neurotransmitter in the mammalian central nervous system, are mediated via signaling by ionotropic glutamate receptors (iGluRs). These ligand-gated ion channels are critical to brain function and are centrally implicated in numerous psychiatric and neurologic disorders. There are different classes of iGluRs with a variety of receptor subtypes in each class that play distinct roles in neuronal functions. The diversity in iGluR subtypes, with their unique functional properties and physiologic roles, has motivated a large number of studies. Our understanding of receptor subtypes has advanced considerably since the first iGluR subunit gene was cloned in 1989, and the research focus has expanded to encompass facets of biology that have been recently discovered and to exploit experimental paradigms made possible by technological advances. Here, we review insights from more than 3 decades of iGluR studies with an emphasis on the progress that has occurred in the past decade. We cover structure, function, pharmacology, roles in neurophysiology, and therapeutic implications for all classes of receptors assembled from the subunits encoded by the 18 ionotropic glutamate receptor genes.

Significance Statement

Glutamate receptors play important roles in virtually all aspects of brain function and are either involved in mediating some clinical features of neurological disease or represent a therapeutic target for treatment. Therefore, understanding the structure, function, and pharmacology of this class of receptors will advance our understanding of many aspects of brain function at molecular, cellular, and system levels and provide new opportunities to treat patients.
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