Functional conservation and species-specific tuning of PIEZO1 mechanotransduction in birds and humans

Birds experience distinct mechanical environments and performance demands, yet how mechanotransduction mechanisms are conserved and quantitatively tuned in avian species remains poorly understood. PIEZO1 is a mechanosensitive cation channel that mediates diverse physiological processes in mammals; however, its functional role in birds has not been directly established. Here, we present a comprehensive electrophysiological comparison of chicken PIEZO1 (gPIEZO1) and human PIEZO1 (hPIEZO1) using heterologous expression systems and native human cells. Using whole-cell and excised outside-out patch-clamp recordings, we show that both gPIEZO1 and hPIEZO1 are robustly activated by membrane stretch and by the synthetic PIEZO1 agonist Yoda1, generating characteristic mechanically activated currents that are potentiated by Yoda1 and inhibited by gadolinium. Single-channel analyses revealed comparable unitary currents for mechanically and chemically evoked currents in both orthologs, indicating conservation of core permeation properties. Notably, gPIEZO1 exhibited significantly greater sensitivity to both mechanical stimulation and Yoda1 than hPIEZO1, revealing species-dependent tuning of PIEZO1 mechanosensitivity. Importantly, in human skin keratinocytes, mechanical stimulation and Yoda1 elicited PIEZO1-like currents that were abolished by siRNA-mediated knockdown of PIEZO1, confirming physiological relevance in a native cellular context. Together, these findings establish PIEZO1 as a functional mechanosensor in birds and illustrate conserved yet quantitatively tuned mechanotransduction across vertebrates.