Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA, 19104, USA.
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA, 19104, USA.
Int J Parasitol Drugs Drug Resist. 2020 Aug;13:1-7. doi: 10.1016/j.ijpddr.2020.02.002. Epub 2020 Mar 24.
Ion channels underlie electrical excitability in cells and are essential for a variety of functions, most notably neuromuscular and sensory activity. They are also validated targets for a preponderance of approved anthelmintic compounds. Transient receptor potential (TRP) channels constitute an ion channel superfamily whose members play important roles in sensory signaling, regulation of ion homeostasis, organellar trafficking, and other key cellular and organismal activities. Unlike most other ion channels, TRP channels are often polymodal, gated by a variety of mechanisms. Furthermore, TRP channels fall into several classes or subtypes based on sequence and structure. Until recently, there had been very little investigation of the properties and functions of TRP channels from parasitic helminths, including schistosomes, but that situation has changed in the past few years. Indeed, it is now clear that at least some schistosome TRP channels exhibit unusual pharmacological properties, and, intriguingly, both a mammalian and a schistosome TRP channel are activated by praziquantel, the current antischistosomal drug of choice. With the latest release of the Schistosoma mansoni genome database, several changes in predicted TRP channel sequences appeared, some of which were significant. This review updates and reassesses the TRP channel repertoire in S. mansoni, examines recent findings regarding these potential therapeutic targets, and provides guideposts for some of the physiological functions that may be mediated by these channels in schistosomes.
离子通道是细胞电兴奋性的基础，对于多种功能至关重要，尤其是神经肌肉和感觉活动。它们也是大多数已批准的驱虫化合物的有效靶点。瞬时受体电位 (TRP) 通道构成离子通道超家族，其成员在感觉信号转导、离子稳态调节、细胞器运输以及其他关键的细胞和机体活动中发挥重要作用。与大多数其他离子通道不同，TRP 通道通常是多模态的，由多种机制门控。此外，TRP 通道根据序列和结构分为几个类别或亚型。直到最近，对寄生虫蠕虫（包括血吸虫）的 TRP 通道的特性和功能的研究还很少，但这种情况在过去几年中发生了变化。事实上，现在很清楚，至少一些血吸虫 TRP 通道表现出异常的药理学特性，而且，有趣的是，一种哺乳动物和一种血吸虫 TRP 通道都被目前首选的抗血吸虫药物吡喹酮激活。随着最新发布的曼氏血吸虫基因组数据库，预测的 TRP 通道序列出现了一些变化，其中一些变化是显著的。这篇综述更新并重新评估了曼氏血吸虫中的 TRP 通道库，检查了这些潜在治疗靶点的最新发现，并为这些通道在血吸虫中可能介导的一些生理功能提供了指导。
