Ablation of ?2?-1 inhibits cell-surface trafficking of endogenous N-type calcium channels in the pain pathway in vivo.

ABSTRACT: The auxiliary ?2? calcium channel subunits play key roles in voltage-gated calcium channel function. Independent of this, ?2?-1 has also been suggested to be important for synaptogenesis. Using an epitope-tagged knockin mouse strategy, we examined the effect of ?2?-1 on CaV2.2 localization in the pain pathway in vivo, where CaV2.2 is important for nociceptive transmission and ?2?-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 ?2?-1 abolishes CaV2.2 cell-surface expression in dorsal root ganglion neurons and dramatically reduces dorsal horn expression. There was no effect of ?2?-1 knockout on other dorsal horn pre- and postsynaptic markers, indicating the primary afferent pathways are not otherwise affected by ?2?-1 ablation.

SUBMITTER: Nieto-Rostro M 

PROVIDER: S-EPMC6305000 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature