Suppression of kainate-evoked AMPA receptor mediated responses by lanthanum in rat sacral dorsal commissural neurons

Neurosignals. Sep-Oct 2004;13(5):258-64. doi: 10.1159/000079340.

Abstract

The effect of lanthanum (La) on kainate (KA) responses in neurons acutely dissociated from the rat sacral dorsal commissural nucleus (SDCN) was investigated using the nystatin-perforated patch-recording configuration under voltage-clamp conditions. The responses to KA were mediated by activation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in SDCN neurons. La(3+) reversibly inhibited KA (100 microM) activated currents (I(KA)) in a concentration-dependent manner over the range from 30 microM to 30 mM, with IC(50) values of 0.64 +/- 0.06 mM at a holding potential (V(H)) of -40 mV. Our further study indicated that the effects of La(3+) on I(KA) were voltage independent. Moreover, the inhibition was not use dependent and was not overcome by increasing the concentration of agonist. These findings indicate that La(3+) is an efficacious inhibitor of AMPA receptor mediated responses which may contribute to its cytotoxic effect.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Animals, Newborn
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • In Vitro Techniques
  • Kainic Acid / pharmacology*
  • Lanthanum / pharmacology*
  • Lumbosacral Plexus / cytology*
  • Membrane Potentials / drug effects
  • Neural Inhibition / drug effects*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Patch-Clamp Techniques / methods
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / physiology*

Substances

  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Receptors, AMPA
  • Lanthanum
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Kainic Acid