A novel activator of Piezo1: Electrophysiological study.

Abstract

Mechanosensitive ion channel Piezo1 plays important roles in diverse physiological processes, including differentiation, angiogenesis, vasodilation, wound healing, and inflammation. To date, three Piezo1 activators (Yoda1, Jedi1, and Jedi2) were discovered through high-throughput screening. These are artificially synthesized chemicals and not pharmacologically authorized, thus having potentials to cause problems when being administrated in human. In this study, we introduce a novel activator of Piezo1 (NAP1) that is a natural component of organisms. The effect of NAP1 on Piezo1 current was tested through electrophysiological recording on Piezo1-deficient (P1KO) HEK293T cells with or without transfection of human Piezo1 (hPiezo1). Without hPiezo1 on P1KO HEK293T, mechanical stimulation failed to activate current, which was still not observable after the application of NAP1 to the cells. However, NAP1 sensitized hPieoz1 currents in various patch configurations. In cell-attached recording, extracellular NAP1 (10, 30, and 100 µM) increased hPiezo1 currents in a dose-dependent manner, shifted the current-stimulus curve leftwards, and increased the pressure sensitivity. However, 100 µM NAP1 didn’t alter the single channel conductance of hPiezo1. In outside-out and whole-cell recordings, NAP1 reversibly enhanced hPiezo1 currents. The association and dissociation times of 100 µM NAP1 measured in the outside-out configuration were approximately 8 seconds. Like Yoda1, NAP1 did not sensitize human Piezo2 in the whole cell configuration. Since NAP1 is biocompatible and orally administrable, it will replace the other Piezo1 activators, with its biocompatibility triggering the vitalization of animal studies involving Piezo1.