Selective loss of slow and enhancement of fast Na+currents in cutaneous afferent dorsal root ganglion neurones following axotomy

Abstract

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.