Piezo channels are mechanosensitive ion channels. Piezo1 is primarily expressed in nonsensory tissues, whereas Piezo2 is predominantly found in sensory tissues, including dorsal root ganglion (DRG) neurons[1].Jedi2 is a Piezo1 activator, but not a specific Piezo2 activator. Jedi2 binds to the mouse Piezo1 proteins with a Kd of 2770 mm. Jedi2 evokes Piezo1-mediated Ca2+ influx. Jedi2 (200 μM) specifically elicits dose-dependent responses in mPiezo1-transfected cells, but not in mPiezo2- or vector-transfected cells. Jedi2 (1 mM) causes an increase in Ca2+ in mCherry-positive HEK293T cells transfected with the mPiezo1-mCherry construct, which also responded to Yoda1 (30 μM). Jedi-induced activation of Piezo1 requires the key mechanotransduction components, including the two extracellular loops in the distal blade and the two leucine residues in the proximal end of the beam[2]. Piezo1 protein was present in endothelium and PVAT of rat aortic and in PVAT of mesenteric artery.The Piezo1 agonists Yoda1 and Jedi2 (1 nM - 10 µM) did not stimulate aortic contraction [max < 10% phenylephrine (PE) 10 µM contraction] or relaxation in tissues + or -PVAT. Depolarizing the aorta by modestly elevated extracellular K+ did not unmask aortic contraction to Yoda1 (max <10% PE 10 µM contraction)[3].
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