Fallah Hamideh P, Ahuja Ekta, Lin Haoquan, Qi Jinlong, He Qian, Gao Shan, An Hailong, Zhang Jian, Xie Yongzhen, Liang Dong
Aurora Biomed Inc., Vancouver, BC, Canada.
Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
Front Pharmacol. 2022 May 24;13:914499. doi: 10.3389/fphar.2022.914499. eCollection 2022.
Transient receptor potential (TRP) proteins are a large group of ion channels that control many physiological functions in our body. These channels are considered potential therapeutic drug targets for various diseases such as neurological disorders, cancers, cardiovascular disease, and many more. The Nobel Prize in Physiology/Medicine in the year 2021 was awarded to two scientists for the discovery of TRP and PIEZO ion channels. Improving our knowledge of technologies for their study is essential. In the present study, we reviewed the role of TRP channel types in the control of normal physiological functions as well as disease conditions. Also, we discussed the current and novel technologies that can be used to study these channels successfully. As such, Flux assays for detecting ionic flux through ion channels are among the core and widely used tools for screening drug compounds. Technologies based on these assays are available in fully automated high throughput set-ups and help detect changes in radiolabeled or non-radiolabeled ionic flux. Aurora's Ion Channel Reader (ICR), which works based on label-free technology of flux assay, offers sensitive, accurate, and reproducible measurements to perform drug ranking matching with patch-clamp (gold standard) data. The non-radiolabeled trace-based flux assay coupled with the ICR detects changes in various ion types, including potassium, calcium, sodium, and chloride channels, by using appropriate tracer ions. This technology is now considered one of the very successful approaches for analyzing ion channel activity in modern drug discovery. It could be a successful approach for studying various ion channels and transporters, including the different members of the TRP family of ion channels.
瞬时受体电位(TRP)蛋白是一大类离子通道,控制着我们身体的许多生理功能。这些通道被认为是治疗各种疾病的潜在药物靶点,如神经系统疾病、癌症、心血管疾病等等。2021年诺贝尔生理学/医学奖授予了两位科学家,以表彰他们对TRP和PIEZO离子通道的发现。提高我们对其研究技术的了解至关重要。在本研究中,我们回顾了TRP通道类型在控制正常生理功能以及疾病状态中的作用。此外,我们还讨论了可用于成功研究这些通道的现有技术和新技术。因此,用于检测通过离子通道的离子通量的通量测定法是筛选药物化合物的核心且广泛使用的工具之一。基于这些测定法的技术可用于全自动高通量设置,并有助于检测放射性标记或非放射性标记的离子通量变化。奥罗拉离子通道阅读器(ICR)基于通量测定的无标记技术工作,可提供灵敏、准确且可重复的测量,以进行与膜片钳(金标准)数据匹配的药物排名。与ICR相结合的非放射性标记的基于痕量的通量测定法,通过使用适当的示踪离子来检测包括钾、钙、钠和氯通道在内的各种离子类型的变化。该技术现在被认为是现代药物发现中分析离子通道活性的非常成功的方法之一。它可能是研究各种离子通道和转运蛋白(包括TRP离子通道家族的不同成员)的成功方法。