Altered expression and function of sodium channels in large DRG neurons and myelinated A-fibers in early diabetic neuropathy in the rat

Differential alterations of sodium channels in small nociceptive C-fiber DRG neurons have been implicated in diabetic neuropathy. In this study, we investigated sodium currents and the expression of sodium channels in large A-fiber DRG neurons in diabetic rats. Compared with controls, large neurons from diabetic rats showed significant increases in both total and TTX-S sodium currents and ∼−15 mV shifts in their voltage-dependent activation kinetics. TTX-R Nav1.9 sodium current was also significantly increased, whereas no alteration of TTX-R Nav1.8 current was observed in neurons from diabetic rats. Sodium current induced by fast- or slow-voltage ramps increased markedly in the diabetic neurons as well. Immunofluorescence studies showed significant increases in the levels and number of large DRG neurons from diabetic rats expressing Nav1.2, Nav1.3, Nav1.7, and Nav1.9 whereas Nav1.8 decreased. We also observed a decrease in the number of nodes of Ranvier expressing Nav1.8 and in staining intensity of Nav1.6 and Nav1.8 at nodes. Our results suggest that alterations of sodium channels occur in large DRG neurons and A-fibers, and may play an important role in diabetic sensory neuropathy.