Tetrodotoxin-resistant sodium channels of dorsal root ganglion neurons arereadily activated in diabetic rats

To clarify the mechanism of hyperalgesia in diabetic neuropathy, we investi gated the effects of streptozocin-induced hyperglycemia on tetrodotoxin-res istant Na+ channel activity of dorsal root ganglion neurons. Experiments we re performed on enzymatically isolated neurons of dorsal root ganglia disse cted from streptozocin-induced diabetic and their age-matched control rats. Membrane currents were recorded using the whole-cell patch-clamp technique . Mean current density of tetrodotoxin-resistant Na+ channels was significa ntly larger in neurons prepared from diabetic rats than in control neurons. Tetrodotoxinresistant Na+ channels were activated at more negative potenti als in diabetic than in control neurons. Curves representing the steady-sta te inactivation and the peak Na+ conductance as a function of membrane pote ntial shifted to the negative side. The changes in gating property of the N a+ channel were observed six weeks after the injection of streptozocin, and still after eight months, indicating that tetrodotoxin-resistant Na+ chann el abnormality starts to develop early and persists during the whole period of diabetes. These results suggest that neurons participating in nociception are highly excitable in diabetic animals. The present results may provide an important clue to the elucidation of hyperalgesia in diabetes. (C) 1999 IBRO. Publis hed by Elsevier Science Ltd.