Sodium currents of large (A beta-type) adult cutaneous afferent dorsal root ganglion neurons display rapid recovery from inactivation before and after axotomy

Voltage-dependent Na-currents were studied, using whole cell voltage clamp, in acutely dissociated, large (mostly A beta -fiber type) cutaneous affere nt dorsal root ganglia neurons (L-4 and L-5) from the adult rat. Cells were dissociated 14-17 days after axotomy. Control and axotomized neurons were identified via the retrograde marker hydroxy-stilbamide (fluorogold) which was injected into the lateral and plantar region of the skin of the foot an d were studied using whole cell patch clamp techniques within 12-20 h of di ssociation and plating. Cells were dissociated 14-17 days after injury. Bot h control and axotomized neurons displayed complex Na-currents composed of components with distinct kinetic and pharmacological properties. The large (48-50 mum diameter) control cutaneous afferent neurons, many of which like ly give rise to myelinated A beta -fibers, exhibited Na-currents with both slow and fast inactivating kinetics. The fast inactivating current in large cutaneous afferent dorsal root ganglion neurons was tetrodotoxin-sensitive and recovered from inactivation similar to four-fold faster at -60 mV (P < 0.001) and similar to six-fold faster at -70 mV (P<0.001) than the tetrodot oxin-sensitive current in small (<less than> 30 mum diameter) neurons. Furt her, while the tetrodotoxin-sensitive currents in smaller dorsal root gangl ion neurons (mainly C-fiber type) reprime approximately four-fold faster fo llowing peripheral axotomy, reprinting of the fast inactivating current in larger cutaneous afferent neurons was not significantly altered following a xotomy. However, while 77% of control large neurons were observed to expres s the slower inactivating, tetrodotoxin-resistant current, only 45% of thes e large neurons did after axotomy. These results indicate that large adult cutaneous afferent dorsal root gang lion neurons (A beta -type) express tetrodotoxin-sensitive Na-currents, whi ch have much faster repriming than Na-currents in small (C-type) neurons, b oth before, and after axotomy. Like small neurons, the majority of large ne urons downregulate the tetrodotoxin-resistant current following sciatic ner ve section. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights re served.