Enhancement of GABAA receptor-mediated Conductances Induced by Nerve Injury in a Subclass of Sensory Neurons. Oyelese, Adetokunbo A., Douglas L. Eng, George B. Richerson and Jeffery D. Kocsis. Department of Neurology, Yale University School of Medicine, New Haven, CT. 06510, Neuroscience Research Center, Department of Veterans Affairs, West Haven, CT. 06516.
APStracts 2:0124N, 1995.
SUMMARY AND CONCLUSIONS
1. The effects of axotomy on the electrophysiologic properties of adult rat dorsal root ganglion (DRG) neurons were studied in order to understand the changes in excitability induced by traumatic nerve injury. Nerve injury was induced in vivo by sciatic nerve ligation with distal nerve transection. Two to four weeks after nerve ligation, a time when a neuroma forms, lumbar (L4 and L5) DRG neurons were removed and placed in short-term tissue culture. Whole-cell patch-clamp recordings were made 5 - 24 hours after plating. 2. DRG neurons were grouped into large (43-65 [mu] m), medium (34-42 [mu] m) and small (20-32 [mu] m) size classes. Large neurons had short duration action potentials with about 60 % having inflections on the falling phase of their action potentials. In contrast, action potentials of medium and small neurons were longer in duration and about 68 % had inflections. 3. Pressure microejection of GABA (100 [mu] M) or muscimol (100 [mu] M) onto voltage- clamped DRG neurons elicited a rapidly desensitizing inward current which was blocked by 200 [mu] M bicuculline. To measure the peak conductance induced by GABA or muscimol, neurons were voltage-clamped at a holding potential of -60 mV, and pulses to -80 mV and -100 mV were applied at a rate of 2.5 or 5 Hz during drug application. Slope conductances were calculated from plots of whole cell current measured at each of these potentials. 4. GABA-induced currents and conductances of control DRG neurons increased progressively with cell diameter. The mean GABA conductance was 36 +/- 10 nS (mean +/- SEM) in small neurons, 124 ? +/- ? 21 nS in medium neurons, and 527 +/- 65 nS in large neurons. 5. After axotomy, medium neurons had significantly larger GABA- induced conductances compared to medium control neurons (390 +/- 50 vs 124 +/- 21; mean +/- SEM; p<0.001). The increase in GABA conductance of medium neurons was associated with a decrease in duration of action potentials. In contrast, small neurons had no change in GABA conductance or action potential duration after ligation. The GABA conductance of large control neurons was highly variable, but ligation resulted in an increase that was significant only for neurons larger than 50 m. The mean action potential duration in large neurons was not significantly changed, but neurons with inflections on the falling phase of the action potential were less common after ligation. There was no difference in resting potential or input resistance between control and ligated groups, except that the resting potential was less negative in small cells following axotomy. 6. Histograms of neuronal diameter distributions were constructed for control and ligated groups. The cell diameter distribution of control and ligated neurons were similar, but the ligated group had a decrease in the proportion of large neurons and a 27 % increase in medium neurons, with no change in the relative proportion of other size classes. The 27 % increase in the number of medium neurons was unlikely to be solely responsible for the 314 % increase in GABA conductance seen in medium neurons after ligation, although some of the observed change could be attributed to a shift of large neurons (and their associated electrophysiologic properties) into the medium group. 7. These results indicate that axotomy resulted in a significant increase in GABAA receptor-mediated conductance in specific size classes of sensory neurons. We hypothesize that this selective increase in GABA conductance results from an injury-induced increase in the density of GABAA receptors on the soma, or a change in the expression of specific GABAA receptor subtypes with different single channel conductances. 

Received 17 November 1994; accepted in final form 3 April 1995.
APS Manuscript Number J726-4.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  1 May 1995.