Subtype-specific reduction of voltage-gated calcium current in medium-sized dorsal root ganglion neurons after painful peripheral nerve injury

Neuroscience. 2011 Apr 14:179:244-55. doi: 10.1016/j.neuroscience.2011.01.049. Epub 2011 Jan 28.


Sensory neurons express a variety of voltage-gated Ca2+ channel subtypes, but reports differ on their proportionate representation, and the effects of painful nerve injury on each subtype are not established. We compared levels of high-voltage activated currents in medium-sized (30-40 μm) dorsal root ganglion neurons dissociated from control animals and those subjected to spinal nerve ligation, using sequential application of semiselective channel blockers (nisoldipine for L-type, SNX-111 or ω-conotoxin GVIA for N-type, agatoxin IVA or ω-conotoxin MVIIC for P/Q-type, and SNX-482 for a component of R-type) during either square wave depolarizations or action potential waveform voltage commands. Using sequential administration of multiple blockers, proportions of total Ca2+ current attributable to different subtypes and the effect of injury depended on the sequence of blocker administration and type of depolarization command. Overall, however, N-type and L-type currents comprised the dominant components of ICa in sensory neurons under control conditions, and these subtypes showed the greatest loss of current following injury (L-type 26-71% loss, N-type 0-51% loss). Further exploration of N-type current identified by its sensitivity to ω-conotoxin GVIA applied alone showed that injury reduced the peak N-type current during step depolarization by 68% and decreased the total charge entry during action potential waveform stimulation by 44%. Isolation of N-type current by blockade of all other subtypes demonstrated a 50% loss with injury, and also revealed an injury-related rightward shift in the activation curve. Non-stationary noise analyses of N-type current in injured neurons revealed unitary channel current and number of channels that were not different from control, which indicates that injury-induced loss of current is due to a decrease in channel open probability. Our findings suggest that diminished Ca2+ influx through N-type and L-type channels may contribute to sensory neuron dysfunction and pain after nerve injury.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / injuries
  • Ganglia, Spinal / metabolism*
  • Ligation
  • Male
  • Neuralgia / metabolism*
  • Neuralgia / physiopathology
  • Patch-Clamp Techniques
  • Peripheral Nerve Injuries
  • Peripheral Nerves / metabolism*
  • Peripheral Nerves / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / metabolism*


  • Calcium Channel Blockers
  • Calcium Channels