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Effects of neuropathy on high-voltage-activated Ca2+ current in sensory neurones

Yang, L. and Stephens, G. J. (2009) Effects of neuropathy on high-voltage-activated Ca2+ current in sensory neurones. Cell Calcium, 46 (4). 248-256 . ISSN 01434160

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To link to this article DOI: 10.1016/j.ceca.2009.08.001

Abstract/Summary

Voltage-dependent Ca2+ channels (VDCCs) have emerged as targets to treat neuropathic pain; however, amongst VDCCs, the precise role of the CaV2.3 subtype in nociception remains unproven. Here, we investigate the effects of partial sciatic nerve ligation (PSNL) on Ca2+ currents in small/medium diameter dorsal root ganglia (DRG) neurones isolated from CaV2.3(−/−) knock-out and wild-type (WT) mice. DRG neurones from CaV2.3(−/−) mice had significantly reduced sensitivity to SNX-482 versusWTmice. DRGs from CaV2.3(−/−) mice also had increased sensitivity to the CaV2.2 VDCC blocker -conotoxin. In WT mice, PSNL caused a significant increase in -conotoxin-sensitivity and a reduction in SNX-482-sensitivity. In CaV2.3(−/−) mice, PSNL caused a significant reduction in -conotoxin-sensitivity and an increase in nifedipine sensitivity. PSNL-induced changes in Ca2+ current were not accompanied by effects on voltagedependence of activation in either CaV2.3(−/−) or WT mice. These data suggest that CaV2.3 subunits contribute, but do not fully underlie, drug-resistant (R-type) Ca2+ current in these cells. In WT mice, PSNL caused adaptive changes in CaV2.2- and CaV2.3-mediated Ca2+ currents, supporting roles for these VDCCs in nociception during neuropathy. In CaV2.3(−/−) mice, PSNL-induced changes in CaV1 and CaV2.2 Ca2+ current, consistent with alternative adaptive mechanisms occurring in the absence of CaV2.3 subunits.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Interdisciplinary centres and themes > Centre for Integrative Neuroscience and Neurodynamics (CINN)
ID Code:1760
Uncontrolled Keywords:Calcium channel, R-type channel, Neuropathy, DRG, SNX-482
Publisher:Elsevier

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