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

Neuroreport. 2000 Aug 3;11(11):2547-51. doi: 10.1097/00001756-200008030-00040.

Abstract

To test the combined effect of high glucose and decreased Na+/K+-pump activity, a condition which closely mimics the diabetic state, on nerve ionic currents, changes in action potential and membrane current induced by high glucose in the presence of ouabain were investigated using voltage clamp analysis in rat single myelinated nerve fibers. In the presence of 0.1 mM ouabain, 30 mM glucose caused a progressive increase in the delayed K+ current as well as persistent decreases in action potential and Na+ current, suggesting 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+-activated 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+ influx through either Ca2+ channels or reverse Na+/Ca2+-exchange, possibly leading to the elevation of Ca2+-activated voltage-dependent K+ channels. Both a decrease in inward Na+ current and an increase in K+ conductance may result in decreased nerve conduction. In addition, a possible increase of axoplasmic Ca2+ concentration may lead to axonal degeneration. These results provide a clue for understanding the pathophysiologic mechanism of diabetic neuropathy.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / metabolism
  • Calcium Channels, N-Type / drug effects
  • Calcium Channels, N-Type / metabolism
  • Charybdotoxin / pharmacology
  • Diabetic Neuropathies / metabolism
  • Diabetic Neuropathies / pathology
  • Diabetic Neuropathies / physiopathology
  • Glucose / metabolism*
  • Glucose / pharmacology*
  • Male
  • Nerve Fibers, Myelinated / drug effects*
  • Nerve Fibers, Myelinated / metabolism*
  • Nerve Fibers, Myelinated / ultrastructure
  • Ouabain / pharmacology
  • Potassium Channels / drug effects*
  • Potassium Channels / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Potassium-Exchanging ATPase / drug effects*
  • Sodium-Potassium-Exchanging ATPase / metabolism

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Channels, L-Type
  • Calcium Channels, N-Type
  • Potassium Channels
  • Charybdotoxin
  • Ouabain
  • Sodium-Potassium-Exchanging ATPase
  • Glucose