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Axotomy- and Autotomy-Induced Changes in Ca2+and K+ Channel Currents of Rat Dorsal Root Ganglion Neurons

Authors: F A, Abdulla; P A, Smith;

Axotomy- and Autotomy-Induced Changes in Ca2+and K+ Channel Currents of Rat Dorsal Root Ganglion Neurons

Abstract

Sciatic nerve section (axotomy) increases the excitability of rat dorsal root ganglion (DRG) neurons. The changes in Ca2+ currents, K+ currents, Ca2+-sensitive K+ current, and hyperpolarization-activated cation current ( I H) that may be associated with this effect were examined by whole cell recording. Axotomy affected the same conductances in all types of DRG neuron. In general, the largest changes were seen in “small” cells and the smallest changes were seen in “large” cells. High-voltage–activated Ca2+-channel current (HVA- I Ba) was reduced by axotomy. Although currents recorded in axotomized neurons exhibited increased inactivation, this did not account for all of the reduction in HVA- I Ba. Activation kinetics were unchanged, and experiments with nifedipine and/or ω-conotoxin GVIA showed that there was no change in the percentage contribution of L-type, N-type, or “other” HVA- I Bato the total current after axotomy. T-type (low-voltage–activated) I Ba was not affected by axotomy. Ca2+-sensitive K+conductance ( g K,Ca) appeared to be reduced, but when voltage protocols were adjusted to elicit similar amounts of Ca2+ influx into control and axotomized cells, I K,Ca(s) were unchanged. After axotomy, Cd2+-insensitive, steady-state K+ channel current, which primarily comprised delayed rectifier K+ current ( I K), was reduced by about 60% in small, medium, and large cells. These data suggest that axotomy-induced increases in excitability are associated with decreases in I K and/or decreases in g K,Ca that are secondary to decreased Ca2+-influx. Because I H was reduced by axotomy, changes in this current do not contribute to increased excitability. The amplitude and inactivation of I Ba in all cell types was changed more profoundly in animals that exhibited self-mutilatory behavior (autotomy). The onset of this behavior corresponded with significant reduction in I Ba of large neurons. This finding supports the hypothesis that autotomy, that may be related to human neuropathic pain, is associated with changes in the properties of large myelinated sensory neurons.

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Keywords

Male, Potassium Channels, Drug Resistance, Electric Conductivity, Axotomy, Rats, Rats, Sprague-Dawley, Ganglia, Spinal, Self Mutilation, Animals, Calcium Channels, Neurons, Afferent, Cadmium

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Found an issue? Give us feedback
selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
179
Top 10%
Top 10%
Top 1%
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