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

Altier, C; Dale, CS; Kisilevsky, AE; Chapman, K; Castiglioni, AJ; Matthews, EA; Evans, RM; ... Zamponi, GW; + view all (2007) Differential role of N-type calcium channel splice isoforms in pain. J NEUROSCI , 27 (24) 6363 - 6373. 10.1523/JNEUROSCI.0307-07.2007.

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Abstract

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.

Type: Article
Title: Differential role of N-type calcium channel splice isoforms in pain
DOI: 10.1523/JNEUROSCI.0307-07.2007
Keywords: pain, calcium channels, N-type, splice isoforms, siRNA, dorsal root ganglion, NEUROPATHIC PAIN, CA2+ CHANNEL, OMEGA-CONOPEPTIDES, PERIPHERAL NEURONS, CA(V)2.2 CHANNELS, ION CHANNELS, MICE LACKING, SPINAL-CORD, RAT MODEL, P-TYPE
UCL classification: UCL > Provost and Vice Provost Offices
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: http://discovery.ucl.ac.uk/id/eprint/177427
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