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.