DIFFERENTIAL-EFFECTS OF NGF AND BDNF ON AXOTOMY-INDUCED CHANGES IN GABA(A)-RECEPTOR-MEDIATED CONDUCTANCE AND SODIUM CURRENTS IN CUTANEOUS AFFERENT NEURONS

The effects of nerve growth factor (NGF) and brain-derived neurotrophi c factor (BDNF) on injury-induced changes in the electrophysiological properties of adult rat cutaneous afferent dorsal root ganglion (DRG) neurons were examined. Whole cell patch-clamp techniques were used to study gamma-aminobutyric acid-A (GABA(A))-receptor-mediated conductanc e, voltage-dependent sodium currents, and action potential waveform in cutaneous afferent neurons (35-60 mu m diam) cultured from control an d axotomized animals. Cutaneous afferent neurons were identified by re trograde labeling with hydroxy-stilbamidine (Fluoro-gold, a fluorescen t retrograde axonal tracer); the sciatic nerve was transected 1 wk aft er Fluoro-gold injection and L-4/L-5 DRG neurons were cultured 2-3 wk after axotomy. NGF, BDNF, or Ringer (vehicle) solution was delivered i n vivo directly to the transected sciatic nerve stump in axotomized ra ts via an osmotic pump. Recordings were obtained from neurons 5-24 h a fter culture. Axotomized neurons from rats treated with vehicle soluti on displayed a twofold increase in GABA-induced conductance and a prom inent reduction in the proportion of neurons expressing action potenti als that had inflections on the falling phase. The expression of kinet ically slow tetrodotoxin (TTX)-resistant sodium current was markedly r educed and an increased expression of kinetically fast TTX-sensitive c urrent was observed in neurons from vehicle-treated, axotomized rats. Treatment with NGF (0.25 mu g/mu l at 12 mu l/day for 14 days) in axot omized animals resulted in an increase in the proportion of neurons ex pressing TTX-resistant, slow sodium currents and inflected action pote ntials, but had no effect on GABA-induced conductance. Treatment with BDNF (0.5 mu g/mu l at 12 mu l/day for 14 days) attenuated the axotomy -induced increase in GABA, receptor-mediated conductance while minimal ly affecting action potential waveform. The observed neurotrophin effe cts occurred independently of cell size changes. These findings indica te a differential regulation of GABAA receptor and sodium channel prop erties in axotomized rat cutaneous afferent neurons by specific neurot rophic factors.