| First Author | Nieto-Rostro M | Year | 2018 |
| Journal | Proc Natl Acad Sci U S A | Volume | 115 |
| Issue | 51 | Pages | E12043-E12052 |
| PubMed ID | 30487217 | Mgi Jnum | J:269262 |
| Mgi Id | MGI:6272184 | Doi | 10.1073/pnas.1811212115 |
| Citation | Nieto-Rostro M, et al. (2018) Ablation of alpha2delta-1 inhibits cell-surface trafficking of endogenous N-type calcium channels in the pain pathway in vivo. Proc Natl Acad Sci U S A 115(51):E12043-E12052 |
| abstractText | The auxiliary alpha2delta calcium channel subunits play key roles in voltage-gated calcium channel function. Independent of this, alpha2delta-1 has also been suggested to be important for synaptogenesis. Using an epitope-tagged knockin mouse strategy, we examined the effect of alpha2delta-1 on CaV2.2 localization in the pain pathway in vivo, where CaV2.2 is important for nociceptive transmission and alpha2delta-1 plays a critical role in neuropathic pain. We find CaV2.2 is preferentially expressed on the plasma membrane of calcitonin gene-related peptide-positive small nociceptors. This is paralleled by strong presynaptic expression of CaV2.2 in the superficial spinal cord dorsal horn. EM-immunogold localization shows CaV2.2 predominantly in active zones of glomerular primary afferent terminals. Genetic ablation of alpha2delta-1 abolishes CaV2.2 cell-surface expression in dorsal root ganglion neurons and dramatically reduces dorsal horn expression. There was no effect of alpha2delta-1 knockout on other dorsal horn pre- and postsynaptic markers, indicating the primary afferent pathways are not otherwise affected by alpha2delta-1 ablation. |
