Functional Characterization of Mechanosensitive Piezo1 Channels in Trigeminal and Somatic Nerves in a Neuron-on-Chip Model.

Nikita Mikhailov,Lidiia Plotnikova,Rashid Giniatullin,Prateek Singh,Riikka H Hämäläinen

doi:10.3390/ijms23031370

Nikita Mikhailov, Lidiia Plotnikova + Show 3 more

Open Access

https://doi.org/10.3390/ijms23031370

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Abstract

Mechanosensitive ion channels, Piezo1 and 2, are activated by pressure and involved in diverse physiological functions, including senses of touch and pain, proprioception and many more. Understanding their function is important for elucidating the mechanosensitive mechanisms of a range of human diseases. Recently, Piezo channels were suggested to be contributors to migraine pain generation. Migraine is typically characterized by allodynia and mechanical hyperalgesia associated with the activation and sensitization of trigeminal ganglion (TG) nerve fibers. Notably, migraine specific medicines are ineffective for other types of pain, suggesting a distinct underlying mechanism. To address, in a straightforward manner, the specificity of the mechanosensitivity of trigeminal vs. somatic nerves, we compared the activity of Piezo1 channels in mouse TG neurons vs. dorsal root ganglia (DRG) neurons. We assessed the functional expression of Piezo1 receptors using a conventional live calcium imaging setup equipped with a multibarrel application system and utilizing a microfluidic chip-based setup. Surprisingly, the TG neurons, despite higher expression of the Piezo1 gene, were less responsive to Piezo1 agonist Yoda1 than the DRG neurons. This difference was more prominent in the chip-based setup, suggesting that certain limitations of the conventional approach, such as turbulence, can be overcome by utilizing microfluidic devices with laminar solution flow.

Highlights

Mechanosensitive channels, Piezo1 and Piezo2, are non-selective Ca2+ permeable channels that transduce mechanical force into neuronal signals via transmembrane ion flux
Human trigeminal ganglion (TG) neurons express mechanosensitive Piezo1 receptors [11] and we have recently demonstrated that the activation of Piezo1 receptors by a selective Piezo1 agonist Yoda1 [12] activates trigeminal neurons and induces meningeal trigeminal nociceptive signaling [13]
We further calculated the proportion of responding cells (=cells with more than 10% increase in fluorescence from baseline at the end of washout recording) and found a non-significant trend of the dorsal root ganglia (DRG) cells to respond more frequently (52 ± 2% in TG vs. 58 ± 3% in DRG, p = 0.1105 by unpaired Student’s t-test)

Summary

Introduction

Mechanosensitive channels, Piezo and Piezo, are non-selective Ca2+ permeable channels that transduce mechanical force into neuronal signals via transmembrane ion flux. Their functions range from sensing touch and pain to the control of plasticity in various tissues. Migraine pain likely originates from cranial meninges [6,7] which are innervated by trigeminal nerve fibers originating from the trigeminal ganglion (TG) neurons [8,9]. Human TG neurons express mechanosensitive Piezo receptors [11] and we have recently demonstrated that the activation of Piezo receptors by a selective Piezo agonist Yoda1 [12] activates trigeminal neurons and induces meningeal trigeminal nociceptive signaling [13]

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