Fig. 8

Illustration of mechanical loading activated-Piezo1 induces opening of Cx43 HCs via PI3K-Akt pathway. Fluid flow shear stress (FFSS) induces the activation of the Piezo1 Channel, increasing the intracellular Ca²⁺ levels, leading to an increase in the activity of both Cx43 HCs and Panx1 channels, allowing the release of ATP. Extracellular ATP activates P2X receptors promoting the entrance of Ca²⁺ into the cytoplasm, holding the activity of Cx43 HCs and Panx1 channels. Active Piezo1 Channel complex could lead to the activation of the AKT pathway and stabilization of active Cx43 HCs in the cell surface. This system could be inactivated by the action of extracellular phosphatases and reducing the ATP levels. The inhibition of Piezo1 channels (Dooku1) and/or AKT pathway (LY) close Cx43 HCs