Selective loss of slow and enhancement of fast Na+ currents in cutaneous afferent dorsal root ganglion neurones following axotomy.
Voltage-dependent Na+ currents were recorded via patch-clamp from identified adult rat lumbar cutaneous dorsal root ganglion (DRG) neurones using whole-cell and bleb-patch-clamp configurations. Na+ currents in DRG neurones studied 18 days after sciatic nerve ligation were compared with those in control neurones. Control neurones tended to have a singular kinetically slow Na+ current or net Na+ current suggestive of two kinetic varieties of channel in a single neurone. Three changes occurred following axotomy: (1) the peak Na+ current increased significantly, (2) kinetically slow TTX-resistant Na+ current, which predominated in controls, was significantly attenuated or lacking altogether, and (3) a singular, TTX-sensitive kinetically fast form of Na+ current predominated. These findings suggest that as part of the response to axonal injury, DRG neurones increase Na+ channel biosynthesis and/or modify preexisting channels such that their kinetics are accelerated. The results are consistent with the idea that axotomized DRG neurones become hyperexcitable due to the emergence of a high density of kinetically fast, pharmacologically distinguishable, Na+ channels in the membrane.
Rizzo
M A
MA
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Kocsis
J D
JD
Waxman
S G
SG
D000818:Animals; D001369:Axons / Q000502:physiology*; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000294:innervation*; D015222:Sodium Channels / Q000502:physiology*
D015222:Sodium Channels