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

被引:48
作者
Everill, B
Cummins, TR
Waxman, SG
Kocsis, JD [1 ]
机构
[1] Dept Vet Affairs Med Ctr, Rehabil Res Ctr 127A, West Haven, CT 06516 USA
[2] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA
关键词
axotomy; nerve crush; sodium channels; cutaneous afferents; fast repriming current; tail currents;
D O I
10.1016/S0306-4522(01)00258-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Voltage-dependent Na-currents were studied, using whole cell voltage clamp, in acutely dissociated, large (mostly A beta -fiber type) cutaneous afferent 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 and were studied using whole cell patch clamp techniques within 12-20 h of dissociation and plating. Cells were dissociated 14-17 days after injury. Both 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 likely 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 tetrodotoxin-sensitive current in small (<less than> 30 mum diameter) neurons. Further, while the tetrodotoxin-sensitive currents in smaller dorsal root ganglion neurons (mainly C-fiber type) reprime approximately four-fold faster following peripheral axotomy, reprinting of the fast inactivating current in larger cutaneous afferent neurons was not significantly altered following axotomy. However, while 77% of control large neurons were observed to express the slower inactivating, tetrodotoxin-resistant current, only 45% of these large neurons did after axotomy. These results indicate that large adult cutaneous afferent dorsal root ganglion neurons (A beta -type) express tetrodotoxin-sensitive Na-currents, which have much faster repriming than Na-currents in small (C-type) neurons, both before, and after axotomy. Like small neurons, the majority of large neurons downregulate the tetrodotoxin-resistant current following sciatic nerve section. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:161 / 169
页数:9
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