Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia; School of Biomedical Sciences, The University of Queensland, St Lucia, QLD 4072, Australia.
Neuropharmacology. 2017 Dec;127:173-184. doi: 10.1016/j.neuropharm.2017.04.042. Epub 2017 Apr 27.
Acid-sensing ion channels (ASICs) are proton-activated cation channels that are expressed in a variety of neuronal and non-neuronal tissues. As proton-gated channels, they have been implicated in many pathophysiological conditions where pH is perturbed. Venom derived compounds represent the most potent and selective modulators of ASICs described to date, and thus have been invaluable as pharmacological tools to study ASIC structure, function, and biological roles. There are now ten ASIC modulators described from animal venoms, with those from snakes and spiders favouring ASIC1, while the sea anemones preferentially target ASIC3. Some modulators, such as the prototypical ASIC1 modulator PcTx1 have been studied in great detail, while some of the newer members of the club remain largely unstudied. Here we review the current state of knowledge on venom derived ASIC modulators, with a particular focus on their molecular interaction with ASICs, what they have taught us about channel structure, and what they might still reveal about ASIC function and pathophysiological roles. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.'
酸敏离子通道（ASICs）是质子激活的阳离子通道，存在于多种神经元和非神经元组织中。作为质子门控通道，它们与许多 pH 值紊乱的病理生理条件有关。从毒液中提取的化合物是迄今为止描述的最有效和选择性的 ASIC 调节剂，因此它们作为研究 ASIC 结构、功能和生物学作用的药理学工具具有不可估量的价值。目前已经从动物毒液中描述了十种 ASIC 调节剂，其中蛇和蜘蛛的调节剂偏向于 ASIC1，而海葵则优先靶向 ASIC3。一些调节剂，如典型的 ASIC1 调节剂 PcTx1，已经得到了深入的研究，而一些新的成员在很大程度上仍未得到研究。本文综述了目前关于毒液衍生的 ASIC 调节剂的知识状况，特别关注它们与 ASIC 的分子相互作用，以及它们在通道结构方面的研究成果，以及它们在 ASIC 功能和病理生理学方面的作用。本文是题为“毒液衍生肽作为药理学工具”的特刊的一部分。
