Sodium currents of large (Abeta-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 Abeta-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 microm diameter) control cutaneous afferent neurons, many of which likely give rise to myelinated Abeta-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 approximately four-fold faster at -60 mV (P<0.001) and approximately six-fold faster at -70 mV (P<0.001) than the tetrodotoxin-sensitive current in small (<30 microm 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, repriming 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 (Abeta-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.
Everill
B
B
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Cummins
T R
TR
Waxman
S G
SG
Kocsis
J D
JD
D000818:Animals; D019771:Axotomy; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000293:injuries / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009437:Neuralgia / Q000378:metabolism* / Q000503:physiopathology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010523:Peripheral Nervous System Diseases / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries / Q000601:surgery; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013266:Stilbamidines; D013779:Tetrodotoxin / Q000494:pharmacology
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D005456:Fluorescent Dyes; D015222:Sodium Channels; D013266:Stilbamidines; D013779:Tetrodotoxin