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Piezo2 channels mediate corneal noxious mechanosensation

AuthorsFernández-Trillo, Jorge; Florez-Paz, D.; Íñigo-Portugués, Almudena; Gónzalez-Gónzalez, Omar; Viana, Félix; Belmonte, Carlos; Gomis, Ana
Issue Date2019
Citation49th Annual Meeting of the Society for Neuroscience (2019)
AbstractThe transduction and encoding of mechanical forces is crucial for many of the most important physiological processes of life. Activation of low threshold mechanoreceptors evokes tactile and proprioceptive sensations, while activation of nociceptors evokes painful sensations. Significant progress has been made in understanding the cellular and molecular transduction mechanisms in touch receptors and proprioceptors. In contrast, much less is known about the transduction of mechanical forces by mammalian nociceptors. Piezo2 is a mechanically-gated ion channel responsible for touch sensation and proprioception. However, mechanosensitivity of skin nociceptors is unaffected in Piezo2-deficient mice. A recent study suggests that Piezo2 is also required for mechanical allodynia, although no consensus has been reached in this aspect of noxious mechanosensation. The cornea is innervated by two classes of trigeminal mechanosensitive nerve terminals, polymodal nociceptors and pure mechano-nociceptors, whose activation evokes pain. However, the transducing channels underlying their mechanosensitivity have not been identified yet. Thus, the cornea appears a simple and well defined sensory organ to investigate the characteristics of the transducing mechanisms underlying mechanosensitivity in sensory neurons evoking mechanical pain sensations. In the mouse cornea, double immunostaining of peripheral nerve branches for Piezo2 and TRPV1 revealed fibers that express exclusively Piezo2 and others that co-express Piezo2 with the polymodal nociceptor ion channel TRPV1. Whole-cell patch-clamp recordings, combined with simultaneous mechanical indentation, performed in cultured mouse corneal neurons retrogradely marked with the dye FM1-43 applied onto the cornea, uncovered pure mechanonociceptor and polymodal nociceptor neurons, identified by their response to capsaicin. Both classes of neurons displayed the three well-defined types of mechanically-activated (MA) currents with distinct kinetics: RA, IA and SA currents. Following their electrophysiological characterization, neurons were fixed in situ and processed for Piezo2 immunocytochemistry. We found that Piezo2 is expressed in neurons that displayed the three types of MA currents. Furthermore, functional results examining a constitutive Piezo2 KO mouse, in which the channel was eliminated exclusively in peripheral sensory neurons, revealed a significant reduction of mechanical responses in different corneal neurons. These findings provide direct evidence for a role of Piezo2 ion channels in mechanotransduction at corneal sensory endings signaling mechanical pain.
DescriptionResumen del póster presentado al 49th Annual Meeting of the Society for Neuroscience, celebrado en Chicago (USA) del 19 al 23 de octubre de 2019.
Appears in Collections:(IN) Comunicaciones congresos
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