Increases in K+ conductance and Ca2+ influx under high glucose with suppressed Na+/K+-pump activity in rat myelinated nerve fibers

To test the combined effect of high glucose and decreased Na+/K+-pump activ ity, a condition which closely mimics the diabetic state, on nerve ionic cu rrents, changes in action potential and membrane current induced by high gl ucose in the presence of ouabain were investigated using voltage clamp anal ysis in rat single myelinated nerve fibers. In the presence of 0.1 mM ouaba in, 30 mM glucose caused a progressive increase in the delayed K+ current a s well as persistent decreases in action potential and Na+ current, suggest ing that Na+/K+ pump plays an important role in preventing the increase in the K+ current. The latter increase was suppressed by a blocker of Ca2+-act ivated K+ channels. Two types of voltage-dependent Ca2+ channel blockers (L and N-type) as well as a Na+/Ca2+-exchange blocker diminished the ouabain- induced increase in K+ conductance. These results suggest that high glucose with suppressed Na+/K+ pump activity might induce an increase of Ca2+ infl ux through either Ca2+ channels or reverse Na+/ Ca2+-exchange, possibly lea ding to the elevation of Ca2+-activated voltage-dependent K+ channels. Both a decrease in inward Na+ current and an increase in K+ conductance may res ult in decreased nerve conduction. In addition, a possible increase of axop lasmic Ca2+ concentration may lead to axonal degeneration. These results pr ovide a clue for understanding the pathophysiologic mechanism of diabetic n europathy. NeuroReport 11:2547-2551 (C) 2000 Lippincott Williams & Wilkins.