| First Author | Brierley SM | Year | 2011 |
| Journal | J Physiol | Volume | 589 |
| Issue | Pt 14 | Pages | 3575-93 |
| PubMed ID | 21558163 | Mgi Jnum | J:189404 |
| Mgi Id | MGI:5445480 | Doi | 10.1113/jphysiol.2011.206789 |
| Citation | Brierley SM, et al. (2011) TRPA1 contributes to specific mechanically activated currents and sensory neuron mechanical hypersensitivity. J Physiol 589(Pt 14):3575-93 |
| abstractText | The mechanosensory role of TRPA1 and its contribution to mechanical hypersensitivity in sensory neurons remains enigmatic. We elucidated this role by recording mechanically activated currents in conjunction with TRPA1 over- and under-expression and selective pharmacology. First, we established that TRPA1 transcript, protein and functional expression are more abundant in smaller-diameter neurons than larger-diameter neurons, allowing comparison of two different neuronal populations. Utilising whole cell patch clamping, we applied calibrated displacements to neurites of dorsal root ganglion (DRG) neurons in short-term culture and recorded mechanically activated currents termed intermediately (IAMCs), rapidly (RAMCs) or slowly adapting (SAMCs). Trpa1 deletion (-/-) significantly reduced maximum IAMC amplitude by 43% in small-diameter neurons compared with wild-type (+/+) neurons. All other mechanically activated currents in small- and large-diameter Trpa1-/- neurons were unaltered. Seventy-three per cent of Trpa1+/+ small-diameter neurons responding to the TRPA1 agonist allyl-isothiocyanate (AITC) displayed IAMCs to neurite displacement, which were significantly enhanced after AITC addition. The TRPA1 antagonist HC-030031 significantly decreased Trpa1+/+ IAMC amplitudes, but only in AITC responsive neurons. Using a transfection system we also showed TRPA1 over-expression in Trpa1+/+ small-diameter neurons increases IAMC amplitude, an effect reversed by HC-030031. Furthermore, TRPA1 introduction into Trpa1-/- small-diameter neurons restored IAMC amplitudes to Trpa1+/+ levels, which was subsequently reversed by HC-030031. In summary our data demonstrate TRPA1 makes a contribution to normal mechanosensation in a specific subset of DRG neurons. Furthermore, they also provide new evidence illustrating mechanisms by which sensitisation or over-expression of TRPA1 enhances nociceptor mechanosensitivity. Overall, these findings suggest TRPA1 has the capacity to tune neuronal mechanosensitivity depending on its degree of activation or expression. |
