Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications
Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications
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DOI：
10.1021/jm501981g
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发表时间：
2015-09-24
影响因子：
7.3
通讯作者：
Kraus, Richard L.
中科院分区：
文献类型：
--
作者：
Ruiz, Manuel de Lera;Kraus, Richard L.
电压门控钠通道（Nays）的巨大治疗潜力过去一直是许多研究的主题，如今也引起了人们的强烈兴趣。 Na(v)1.7 通道最近受到了广泛关注，因为它们参与伤害感受的基因得到了强有力的验证。在这里，我们总结了 Na-v 领域的研究现状，并介绍了不同 Na-v 通道亚型的分子结构、一般生理学和药理学方面最相关的最新进展。我们讨论 Na-v 通道配体，例如小分子、从动物毒液中分离的毒素以及最近鉴定的 Na(v)1.7 选择性抗体。此外，我们回顾了 Na-v 通道 a 亚基上的八个特征配体结合位点。最后，我们研究了 Na-v 配体可能的治疗应用，并提供了当前临床研究的最新情况。
The tremendous therapeutic potential of voltage-gated sodium channels (Nays) has been the subject of many studies in the past and is of intense interest today. Na(v)1.7 channels in particular have received much attention recently because of strong genetic validation of their involvement in nociception. Here we summarize the current status of research in the Na-v field and present the most relevant recent developments with respect to the molecular structure, general physiology, and pharmacology of distinct Na-v channel subtypes. We discuss Na-v channel ligands such as small molecules, toxins isolated from animal venoms, and the recently identified Na(v)1.7-selective antibody. Furthermore, we review eight characterized ligand binding sites on the Na-v channel a subunit. Finally, we examine possible therapeutic applications of Na-v ligands and provide an update on current clinical studies.