Resting membrane potential in 41A3 mouse neuroblastoma cells. Effect of increased glucose and galactose...

Neuroblastoma cells were used to examine the effect of high concentrations of glucose or galactose and accumulation of polyols on the resting membrane potential. Polyol levels are increased and myo-inositol content decreased when neuroblastoma cells are chronically exposed to media containing 30 mM glucose or 30 mM galactose compared to cells grown in media containing 30 mM fructose. Furthermore, the 6 h accumulation and incorporation into phospholipid of extracellular myo-inositol is decreased in cells exposed to media containing 30 mM glucose or 30 mM galactose compared to cells grown in media containing 30 mM fructose. The resting membrane potential was determined by examining the steady-state accumulation of the lipophilic cation tetra[3H]phenylphosphonium bromide (TPP+). The resting membrane potential of cells grown in media containing 30 mM fructose is about -70 mV which is very similar to the resting membrane potential of cells grown in unsupplemented media. The resting membrane potential is significantly decreased in cells grown in media containing 30 mM glucose or 30 mM galactose. myo-Inositol metabolism and content and polyol levels are maintained at near normal values and the resting membrane potential is improved when media containing 30 mM glucose or 30 mM galactose are supplemented with 0.4 mM sorbinil. Acute exposure of neuroblastoma cells to 2 mM ouabain had no significant effect on [3H]TPP+ accumulation. This suggests that acute inhibition of Na+/K+ pump activity does not decrease the resting membrane potential of neuroblastoma cells. The decrease in resting membrane potential may be induced by the metabolic abnormalities and/or chronic decrease in Na+/K+ pump activity which occur when neuroblastoma cells are chronically exposed to increased glucose or galactose concentrations.