Effects of neuropathy on high-voltage-activated Ca(2+) current in sensory neurones

Cell Calcium. 2009 Oct;46(4):248-56. doi: 10.1016/j.ceca.2009.08.001. Epub 2009 Sep 1.


Voltage-dependent Ca(2+) channels (VDCCs) have emerged as targets to treat neuropathic pain; however, amongst VDCCs, the precise role of the Ca(V)2.3 subtype in nociception remains unproven. Here, we investigate the effects of partial sciatic nerve ligation (PSNL) on Ca(2+) currents in small/medium diameter dorsal root ganglia (DRG) neurones isolated from Ca(V)2.3(-/-) knock-out and wild-type (WT) mice. DRG neurones from Ca(V)2.3(-/-) mice had significantly reduced sensitivity to SNX-482 versus WT mice. DRGs from Ca(V)2.3(-/-) mice also had increased sensitivity to the Ca(V)2.2 VDCC blocker omega-conotoxin. In WT mice, PSNL caused a significant increase in omega-conotoxin-sensitivity and a reduction in SNX-482-sensitivity. In Ca(V)2.3(-/-) mice, PSNL caused a significant reduction in omega-conotoxin-sensitivity and an increase in nifedipine sensitivity. PSNL-induced changes in Ca(2+) current were not accompanied by effects on voltage-dependence of activation in either Ca(V)2.3(-/-) or WT mice. These data suggest that Ca(V)2.3 subunits contribute, but do not fully underlie, drug-resistant (R-type) Ca(2+) current in these cells. In WT mice, PSNL caused adaptive changes in Ca(V)2.2- and Ca(V)2.3-mediated Ca(2+) currents, supporting roles for these VDCCs in nociception during neuropathy. In Ca(V)2.3(-/-) mice, PSNL-induced changes in Ca(V)1 and Ca(V)2.2 Ca(2+) current, consistent with alternative adaptive mechanisms occurring in the absence of Ca(V)2.3 subunits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels, N-Type / genetics
  • Calcium Channels, N-Type / metabolism*
  • Calcium Channels, R-Type / genetics
  • Calcium Channels, R-Type / metabolism
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Ganglia, Spinal / metabolism
  • In Vitro Techniques
  • Ion Channel Gating*
  • Mice
  • Mice, Knockout / metabolism
  • Nociceptors / metabolism*
  • Patch-Clamp Techniques
  • Sciatic Neuropathy / physiopathology*


  • Cacna1b protein, mouse
  • Cacna1e protein, mouse
  • Calcium Channels, N-Type
  • Calcium Channels, R-Type
  • Cation Transport Proteins
  • Calcium