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Differential role of N-type calcium channel splice isoforms in pain.

Authors: Altier, C  Dale, CS  Kisilevsky, AE  Chapman, K  Castiglioni, AJ  Matthews, EA  Evans, RM  Dickenson, AH  Lipscombe, D  Vergnolle, N  Zamponi, GW 
Citation: Altier C, etal., J Neurosci. 2007 Jun 13;27(24):6363-73.
Pubmed: (View Article at PubMed) PMID:17567797
DOI: Full-text: DOI:10.1523/JNEUROSCI.0307-07.2007

N-type calcium channels are essential mediators of spinal nociceptive transmission. The core subunit of the N-type channel is encoded by a single gene, and multiple N-type channel isoforms can be generated by alternate splicing. In particular, cell-specific inclusion of an alternatively spliced exon 37a generates a novel form of the N-type channel that is highly enriched in nociceptive neurons and, as we show here, downregulated in a neuropathic pain model. Splice isoform-specific small interfering RNA silencing in vivo reveals that channels containing exon 37a are specifically required for mediating basal thermal nociception and for developing thermal and mechanical hyperalgesia during inflammatory and neuropathic pain. In contrast, both N-type channel isoforms (e37a- and e37b-containing) contribute to tactile neuropathic allodynia. Hence, exon 37a acts as a molecular switch that tailors the channels toward specific roles in pain.


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RGD Object Information
RGD ID: 1626313
Created: 2007-07-31
Species: All species
Last Modified: 2007-07-31
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.