2.3.2. GPCR Regulation of Piezo Channels

Mechanically activated and rapidly adapting currents in DRG neurons are carried by Piezo2 channels [108] and get sensitized by the activation of B2 bradykinin receptors, an effect that appears to involve PKA as well as PKC [118]. Akin currents are enhanced in the presence of ATP and UTP which act most likely through an activation of P2Y2 receptors [119]. Likewise, mechanically activated and rapidly adapting currents in DRG neurons as well as currents in cells expressing recombinant Piezo2 channels are enhanced by intracellular GTP or GTP*γ*S which both lead to the activation of G proteins [120]. This confirms that the function of mechanosensitive Piezo2 channels

can be enhanced by inflammatory mediators acting on GPCRs. Interestingly, Piezo2 channels can be inhibited by a depletion of membrane PIP2, and this mechanism is believed to underlie the reduction of mechanically activated rapidly adapting currents in DRG neurons in response to an activation of TRPV1 by capsaicin [121]. Why such an effect cannot be observed in DRG neurons during the activation of G*αq*-linked GPCRs, such as B2 bradykinin and P2Y2 receptors [118,119], remains open for future investigation.
