# KCa3.1 Inhibition Abrogates Suppression of Cell Migration and F-Actin Assembly Caused by Selective PIEZO1 Activation in Transformed Mouse Fibroblasts

## TL;DR

This study shows that blocking KCa3.1 channels cancels the effects of PIEZO1 activation on cell movement and actin structure in mouse fibroblasts.

## Contribution

The novel finding is that KCa3.1 channels are critical downstream effectors of PIEZO1 activation in transformed fibroblasts.

## Key findings

- TRAM-34, a KCa3.1 blocker, abrogates Yoda1-induced F-actin assembly and fibroblast migration.
- PIEZO1 activation effects depend on KCa3.1 channels in transformed mouse fibroblasts.
- KCa3.1 channels are primary downstream effectors of PIEZO1 signaling in these cells.

## Abstract

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.