Calcium channel antagonists attenuate NMDA receptor-mediated neurotoxicity of retinal ganglion cells in culture

Brain Res. 1991 Jun 14;551(1-2):297-302. doi: 10.1016/0006-8993(91)90944-q.

Abstract

Dihydropyridine calcium channel antagonists block a prolonged or 'L-type' component of voltage-dependent Ca2+ current in patch-clamp recordings of postnatal rat retinal ganglion cells. In the present study on these neurons, calcium channel antagonists were found at 500-1000 nM concentrations to attenuate the early rise in [Ca2+]i and the subsequent toxic effects of exogenous glutamate, N-methyl-D-aspartate (NMDA), or an endogenous glutamate-related compound present in the retinal cultures. Previous data have shown that the neurotoxicity engendered by these agents can also be prevented by selective NMDA antagonists. The present observations raise the possibility, at least in this preparation, that activation of both voltage-dependent calcium channels and NMDA receptor-operated channels contribute to the injurious effects triggered by molecules binding to the NMDA receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Glutamates / pharmacology
  • Glutamates / physiology
  • Glutamic Acid
  • N-Methylaspartate / pharmacology
  • Nifedipine / pharmacology
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / physiology*

Substances

  • Calcium Channel Blockers
  • Glutamates
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • N-Methylaspartate
  • Nifedipine
  • Calcium