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| Item Type: | Article |
|---|---|
| Title: | Mechanically-gated currents in mouse sensory neurons lacking PIEZO2 |
| Creators Name: | Sánchez-Carranza, Oscar, Bégay, Valérie, Chakrabarti, Sampurna, Pampols-Perez, Mireia, Wang, Lin, García-Contreras, Jonathan Alexis, Hammes, Annette and Lewin, Gary R. |
| Abstract: | Touch sensation starts with the opening of mechanically-gated activated ion channels at neuroglial endings of mechanoreceptors in the skin. The function of around half of low threshold mechanoreceptors is dependent on the presence of the mechanically gated ion channel PIEZO2. It has been reported that particularly rapidly-adapting mechanosensitive currents (RA-currents) in the cell bodies of acutely cultured sensory neurons are dependent on PIEZO2. Here we re-examined this question by making a quantitative study of mechanically-gated currents activated by substrate deflection in sensory neurons lacking PIEZO2. We characterized mechanically-gated currents from embryonic and post-natal sensory neurons, taken from global Piezo2(-/-) or Piezo2 conditional knockouts (Piezo2(cko)), respectively. Surprisingly in both models, Piezo2 gene deletion was not associated with any significant reduction in the sensitivity or incidence of mechanosensitive currents compared to wild type controls. There was, however, a moderate reduction in the incidence of RA-currents with very fast activation and inactivation kinetics in both embryonic Piezo2(-/-) and juvenile Piezo2(cKO) mice. These results show that PIEZO2 channels are not the only mechanosensitive channels mediating RA-currents in sensory neurons. Furthermore, our data suggest that the phenotypes associated with Piezo2 loss of function alleles may sometimes be due to secondary effects of gene deletion, for example, by changing the developmental trajectory of sensory neurons. Emphasis should be put on the diversity of mechanosensitive ion channel function in sensory neurons which needs to be further elucidated. SIGNIFICANCE: The mechanosensitive ion channel PIEZO2 has been proposed to be the major mechanically-gated ion channel for the transduction of touch. We used patch-clamp electrophysiology to measure mechanically gated currents in sensory neurons lacking PIEZO2 channels using two distinct genetic strategies. Piezo2 gene deletion was associated with a moderate reduction in the frequency of very rapidly inactivating mechanosensitive currents in early post-natal sensory neurons. No significant reduction in the sensitivity or incidence of mechanosensitive currents was observed. These data challenge the idea that PIEZO2 channels are the main transducers of force in sensory neurons, at least via substrate deflection. Other interpretations of loss of function phenotypes, including the possibility that early loss of PIEZO2 could alter developmental trajectories of sensory neurons to impair mechanoreceptor function, should be considered. |
| Keywords: | Cellular Mechanotransduction, Ion Channel Gating, Ion Channels, Knockout Mice, Mechanical Phenomena, Sensory Receptor Cells, Animals, Mice |
| Source: | Biophysical Journal |
| ISSN: | 0006-3495 |
| Publisher: | Elsevier / Biophysical Society |
| Volume: | 124 |
| Number: | 24 |
| Page Range: | 4543-4550 |
| Date: | 16 December 2025 |
| Official Publication: | https://doi.org/10.1016/j.bpj.2025.10.042 |
| PubMed: | View item in PubMed |
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