KCa3.1 Inhibition Abrogates Suppression of Cell Migration and F-Actin Assembly Caused by Selective PIEZO1 Activation...

PIEZO1 are Ca²⁺-permeable mechanogated channels that play a crucial role in numerous fundamental cellular responses. Ca²⁺ influx via PIEZO1 could control the activity of various Ca²⁺-dependent molecules within the cells, thus activating Ca²⁺-dependent signaling processes and reactions. Previously, we demonstrated Ca²⁺-mediated coupling between PIEZO1 and KCa channels in the plasma membranes of transformed mouse fibroblasts, where a Ca²⁺ influx through PIEZO1 stimulates the activity of functionally co-localized KCa channels. Importantly, the selective PIEZO1 activator Yoda1 inhibited transformed fibroblast migration, induced F-actin assembly, and stress fiber formation. However, the impact of PIEZO1-KCa channel coupling on the observed effects remains unknown. Here, we performed the molecular identification of KCa channels in transformed mouse fibroblasts. Importantly, TRAM-34, a specific KCa3.1 channel blocker, abrogated the effect of Yoda1 on F-actin organization and fibroblast motility. We conclude that KCa3.1 channels in the plasma membrane are primary downstream effectors and critical contributors to the decrease in transformed fibroblast migration and F-actin assembly caused by selective PIEZO1 activation.