Qiao Min, Penttinen Reetta, Coli Ariel, Murciano Nicoletta, Maurer Felix M, Wagner Christian, Rotordam Maria Giustina, Kaestner Lars
Theoretical Medicine and Biosciences, Medical Faculty, Saarland University, 66421 Homburg, Germany.
Dynamics of Fluids, Experimental Physics, Faculty of Natural Science and Technology, Saarland University, 66123 Saarbrücken, Germany.
Biomolecules. 2025 Aug 1;15(8):1110. doi: 10.3390/biom15081110.
Piezo1 is a mechanosensitive non-selective cation channel. Genetic alterations of the channel result in a hematologic phenotype named Hereditary Xerocytosis. With Yoda1 and, more recently, Yoda2, compounds to increase the activity of Piezo1 have become available. However, their concrete effect depends on the nano environment of the channel and hence on the cell type. Here we compare the potency of Yoda1 and Yoda2 in red blood cells (RBCs). We investigate the effect of the compounds on direct channel activity using automated patch clamp, as well as the secondary effects of channel activation on signalling molecules and cellular response. In terms of signalling, we investigate the temporal response of the second messenger Ca, and in terms of cellular response, the activity of the Gárdos channel. The opening of the Gárdos channel leads to a hyperpolarisation of the RBCs, which is measured by the Macey-Bennekou-Egée (MBE) method. Although the interpretation of the data is not straightforward, we discuss the results in a physiological context and provide recommendations for the use of Yoda1 and Yoda2 to investigate RBCs.
Piezo1是一种机械敏感的非选择性阳离子通道。该通道的基因改变会导致一种名为遗传性口形细胞增多症的血液学表型。有了Yoda1以及最近的Yoda2，能够增强Piezo1活性的化合物已经出现。然而，它们的具体效果取决于通道的纳米环境，因此也取决于细胞类型。在此，我们比较了Yoda1和Yoda2在红细胞（RBC）中的效力。我们使用自动膜片钳研究这些化合物对直接通道活性的影响，以及通道激活对信号分子和细胞反应的次级效应。在信号传导方面，我们研究第二信使Ca的时间响应，在细胞反应方面，研究加尔多斯通道的活性。加尔多斯通道的开放会导致红细胞超极化，这通过梅西 - 本内科 - 埃热（MBE）方法进行测量。尽管数据解读并非直截了当，但我们在生理背景下讨论结果，并为使用Yoda1和Yoda2研究红细胞提供建议。
