Dual action of Dooku1 on PIEZO1 channel in human red blood cells

PIEZO1 is a mechanosensitive non-selective cation channel, present in many cell types including Red Blood Cells (RBCs). Together with the Gárdos forms RBCs tandem that participates rapid adjustment of volume. The pharmacology allowing functional studies roles has only recently been developed, Yoda1 as widely used agonist. In 2018, analogues were step towards an improved understanding and functions. Among these, Dooku1 was most promising antagonist Yoda1-induced effects, without having any ability to activate channels. Since then, various antagonize effects. study using RBCs, shows apparent IC 50 on effects 90.7 µM, one order magnitude above previously reported data other types. Unexpectedly, it able, by itself , produce entry calcium sufficient trigger channel activation. Moreover, evoked rise intracellular sodium concentrations, suggesting targets channel. abolished upon GsMTx4, known blocker, indicating likely PIEZO1. Our observations lead conclusion behaves agonist RBC membrane, similarly but lower potency. Taken together, these results show must be interpreted care especially due unique characteristics membrane associated cytoskeleton.