Nieto-Rostro, M;
Ramgoolam, K;
Pratt, WS;
Kulik, A;
Dolphin, AC;
(2018)
Ablation of α_{2}δ-1 inhibits cell-surface trafficking of endogenous N-type calcium channels in the pain pathway in vivo.
Proceedings of the National Academy of Sciences of the United States of America
, 115
(51)
E12043-E12052.
10.1073/pnas.1811212115.
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Abstract
The auxiliary α_{2}δ calcium channel subunits play key roles in voltage-gated calcium channel function. Independent of this, α_{2}δ-1 has also been suggested to be important for synaptogenesis. Using an epitope-tagged knockin mouse strategy, we examined the effect of α_{2}δ-1 on Ca_{V}2.2 localization in the pain pathway in vivo, where Ca_{V}2.2 is important for nociceptive transmission and α_{2}δ-1 plays a critical role in neuropathic pain. We find Ca_{V}2.2 is preferentially expressed on the plasma membrane of calcitonin gene-related peptide-positive small nociceptors. This is paralleled by strong presynaptic expression of Ca_{V}2.2 in the superficial spinal cord dorsal horn. EM-immunogold localization shows Ca_{V}2.2 predominantly in active zones of glomerular primary afferent terminals. Genetic ablation of α_{2}δ-1 abolishes Ca_{V}2.2 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 α_{2}δ-1 ablation.
Type: | Article |
---|---|
Title: | Ablation of α_{2}δ-1 inhibits cell-surface trafficking of endogenous N-type calcium channels in the pain pathway in vivo |
Location: | United States |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1073/pnas.1811212115 |
Publisher version: | https://doi.org/10.1073/pnas.1811212115 |
Language: | English |
Additional information: | © 2018 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (https://creativecommons.org/licenses/by/4.0/). |
Keywords: | calcium channel, primary afferent, auxiliary subunit, N-type, trafficking |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
URI: | https://discovery.ucl.ac.uk/id/eprint/10063323 |




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