Figure 1.
Summary of signaling pathways regulating Piezo channels. Activation of TRPV1 channels by capsaicin leads to a massive Ca2+ influx, which activated PLCδ isoforms. The concomitant robust decrease in PI(4,5)P2 and PI(4)P levels inhibits Piezo channel activity. Activation of Gq-coupled GPCR-s lead to activation of PLCβ isoforms, with only a modest decrease in PI(4,5)P2 levels, which is not enough to inhibit channel activity, and the downstream activation of PKC will stimulate Piezo2 activity. Activation Gs-coupled receptors potentiate Piezo2 channel activity, via the EPAC pathway. Activation of PKA may also contribute to potentiation of channel activity.