Inhibition of Na+/Ca2+ exchange enhances delayed neuronal death elicited by glutamate in cerebellar granule cell cultures

Brain Res. 1991 May 10;548(1-2):322-5. doi: 10.1016/0006-8993(91)91141-m.

Abstract

Experiments have been carried out on the primary cerebellar granule cell cultures from 7- to 8-day-old Wistar rats. To study a possible contribution of Na+/Ca2+ exchange to the toxic effect of glutamate, two amiloride derivatives, 3',4'-dichlorobenzamil (DCB) and 5-(N-4-chlorobenzyl)-2',4'-dimethylbenzamil (CBDMB), known to be the potent inhibitors of this exchange system, were used. Addition of DCB or CBDMB (at 30 and 10 microM, respectively) to a 25 microM glutamate solution dramatically enhanced the delayed neuronal death observed during the 4 h after termination of glutamate treatment. Similar but insignificantly smaller effects were obtained when these agents were added to the cultures in the post-glutamate period. Removal of Na+ (by substituting for choline chloride) from the external Mg2+-free solution in the post-glutamate period also enhanced a delayed neuronal damage. The data obtained suggest that Na+/Ca2+ exchanger does not constitute the route for Ca2+ entry during the post-glutamate period but, on the contrary, attenuates glutamate neurotoxicity providing Ca2+ extrusion from the cells under the conditions of a sustained Ca2+ influx.

MeSH terms

  • Amiloride / analogs & derivatives*
  • Amiloride / pharmacology
  • Animals
  • Calcium / metabolism*
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / physiology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cerebellum / cytology*
  • Cerebellum / drug effects
  • Cerebellum / physiology
  • Cytoplasmic Granules / drug effects
  • Cytoplasmic Granules / ultrastructure
  • Glutamates / pharmacology*
  • Glutamic Acid
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / physiology
  • Rats
  • Rats, Inbred Strains
  • Sodium-Calcium Exchanger

Substances

  • Carrier Proteins
  • Glutamates
  • Sodium-Calcium Exchanger
  • 3',4'-dichlorobenzamil
  • 5-(N-4-chlorobenzyl)-N-(2',4'-dimethyl)benzamil
  • Glutamic Acid
  • Amiloride
  • Calcium