Ablation of α2δ-1 inhibits cell-surface trafficking of endogenous N-type calcium channels in the pain pathway in vivo : = Ablation of [alpha]2[delta]-1 inhibits cell-surface trafficking of endogenous N-type calcium channels in the pain pathway in vivo
Abstract: The auxiliary α2δ calcium channel subunits play key roles in voltage-gated calcium channel function. Independent of this, α2δ-1 has also been suggested to be important for synaptogenesis. Using an epitope-tagged knockin mouse strategy, we examined the effect of α2δ-1 on CaV2.2 localization in the pain pathway in vivo, where CaV2.2 is important for nociceptive transmission and α2δ-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 α2δ-1 abolishes CaV2.2 cell-surface expression in dorsal root ganglion neurons and dramatically reduces dorsal horn expression. There was no effect of α2δ-1 knockout on other dorsal horn pre- and postsynaptic markers, indicating the primary afferent pathways are not otherwise affected by α2δ-1 ablation
- Alternative title
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Ablation of [alpha]2[delta]-1 inhibits cell-surface trafficking of endogenous N-type calcium channels in the pain pathway in vivo
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Proceedings of the National Academy of Sciences of the United States of America. - 115, 51 (2018) , E12043-E12052, ISSN: 0027-8424
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2019
- Creator
- DOI
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10.1073/pnas.1811212115
- URN
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urn:nbn:de:bsz:25-freidok-1474145
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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25.03.2025, 1:47 PM CET
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Nieto-Rostro, Manuela
- Ramgoolam, Krishma
- Pratt, Wendy S.
- Kulik, Akos
- Dolphin, Annette C.
- Albert-Ludwigs-Universität Freiburg. Physiologisches Institut
- Universität
Time of origin
- 2019
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