Faculty Collaboration Database

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

Date

02/01/2011

Pubmed ID

21277351

Pubmed Central ID

PMC3209503

DOI

10.1016/j.neuroscience.2011.01.049

Scopus ID

2-s2.0-79952622183 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

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.

Author List

McCallum JB, Wu HE, Tang Q, Kwok WM, Hogan QH

Authors

Quinn H. Hogan MD Professor in the Anesthesiology department at Medical College of Wisconsin
Wai-Meng Kwok PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Action Potentials
Animals
Calcium Channel Blockers
Calcium Channels
Ganglia, Spinal
Ligation
Male
Neuralgia
Patch-Clamp Techniques
Peripheral Nerve Injuries
Peripheral Nerves
Rats
Rats, Sprague-Dawley
Sensory Receptor Cells