Regulation of Piezo Channels by Cellular Signaling Pathways

The recently identified mechanically activated Piezo1 and Piezo2 channels play major roles in various aspects of mechanosensation in mammals, and their mutations are associated with human diseases. Recent reports show that activation of cell surface receptors coupled to heterotrimeric Gq proteins increase the sensitivity of Piezo2 channels to mechanical stimuli. Activation of the cyclic adenosine monophosphate pathway was also shown to potentiate Piezo2 channel activity. This phenomenon may play a role in mechanical allodynia or hyperalgesia during inflammation. Both Piezo1 and Piezo2 channels are inhibited upon depletion of plasma membrane phosphoinositides, in response to phospholipase C activation by Ca²⁺ influx via the transient receptor potential vanilloid 1 channels. This review will discuss current knowledge on regulation of Piezo channels by these intracellular signaling pathways.