Increased Depolarization‐Induced Cytosolic CA2+ Signal In Rat Dorsal Root Ganglion Neurons Under High Glucose With Suppressed NA+/K+ Pump Activity

Abstract

Hyperglycemia and its associated Na+/K+ pump activity has been implicated in the development of diabetic neuropathy. We recently reported that high glucose in the presence of ouabain induced a progressive increase in the delayed K+ current which was suppressed by a blocker of Ca2+‐activated K+ channels and blockers of Ca2+ channels in rat single myelinated nerve fibers, suggesting an increase of cytosolic free Ca2+ concentration ([Ca2+]i). However, the influences of high glucose with ouabain on [Ca2+]i in sensory neurons remain to be elucidated. The present study was undertaken to examine the modulation of depolarization‐induced Ca2+ transients by high glucose and ouabain in isolated adult rat dorsal root ganglion (DRG) neurons using the fluorescent Ca2+ indicator fura‐2. Bath application of KCl (50 mM) evoked a rapid increase in [Ca2+]i through voltage dependent Ca2+ channels ([Ca2+]i: 154.2 ± 22.5 nM). This increase was enhanced under high glucose (30 mM D‐glucose) in the presence of ouabain (100 M) ([Ca2+]i: 764.8 ± 210.1 nM). We conclude that a combination of high glucose and decreased Na+/K+ pump activity leads to an increase in [Ca2+]i in rat DRG neurons, thereby resulting in nerve dysfunction.