Hot Topic: Piezo channels and mechano-transduction in sensory neurons

Piezo channels (Piezo1 and Piezo2) are excitatory ion channels which respond directly to a variety of forms of mechanical stimuli. Two recent papers describe some of the critical roles of Piezo channels in sensory neuron transduction (1, 2). In the first, Murthy et al. (1) demonstrate that Piezo2 mediates both inflammatory and nerve-injury sensitized mechanical pain in mice. In the second, Zeng et al. (2), show that both Piezo1 and Piezo2 are responsible for the baro-receptor reflex that regulates blood pressure and cardiac function.

For researchers interested in studying the roles of Piezo channels in mechano-transduction, useful pharmacological tools, at least for Piezo1, in the form of allosteric activators (3) and an inhibitor (4), have already emerged. Named Yoda1, Jedi1, Jedi2 and Dooku1, they are. May the force………

Comments by Alistair Mathie (@AlistairMathie) and Emma L. Veale (@Ve11Emma), The Medway School of Pharmacy

(1) Murthy SE et al. (2018). The mechanosensitive ion channel Piezo2 mediates sensitivity to mechanical pain in mice. Sci Transl Med. doi: 10.1126/scitranslmed.aat9897. [PMID: 30305457].
(2) Zeng WZ et al. (2018). PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex. Science doi: 10.1126/science.aau6324. [PMID: 30361375].
(3) Wang Y et al. (2018). A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel. Nat Commun. 9(1):1300. doi: 10.1038/s41467-018-03570-9. [PMID: 29610524].
(4) Evans EL et al. (2018). Yoda1 analogue (Dooku1) which antagonizes Yoda1-evoked activation of Piezo1 and aortic relaxation. Br J Pharmacol. 175(10):1744-1759. doi: 10.1111/bph.14188. [PMID: 29498036].

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