Thiocyanate ions selectively antagonize AMPA-evoked responses in Xenopus laevis oocytes microinjected with rat brain mRNA

Br J Pharmacol. 1993 Jul;109(3):779-87. doi: 10.1111/j.1476-5381.1993.tb13642.x.


1 Responses to kainate (KA), willardiine and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were recorded from rat brain mRNA-injected Xenopus laevis oocytes by use of a two-electrode voltage clamp. 2 Thiocyanate (SCN-; 50 microM-4 mM) ions reversibly and selectively inhibited the membrane current responses to AMPA in a non-competitive manner without affecting KA or willardiine-induced responses. 3 The inhibition of AMPA-induced responses by SCN- was dependent on the SCN- concentration with an estimated IC50 of 1 mM. The antagonism was not dependent on the AMPA concentration. 4 The response to a high concentration of AMPA (100-200 microM) exhibited a peak inward current which declined to a steady-state. SCN- inhibited the steady-state current more than the peak response. The inhibition was unaffected by prior incubation with concanavalin-A (Con-A; 10 microM). 5 Responses to KA were antagonized by AMPA in a competitive manner, suggesting that both agonists may activate a common receptor-channel complex. This interaction between two non-NMDA agonists was not affected by the SCN(-)-induced inhibition of the AMPA response. 6 AMPA-induced responses recorded from large cultured cerebellar neurones by whole-cell recording were also inhibited by SCN- in a non-competitive manner. The AMPA-induced peak current was less affected than the steady-state response. 7 We conclude that SCN- can inhibit the response to AMPA in expressed non-NMDA receptors in Xenopus oocytes and also in native receptors in cultured cerebellar neurones. One possible mechanism of action for SCN- inhibition of responses to AMPA may involve a Con-A-insensitive, non-NMDA receptor-mediated desensitization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / analogs & derivatives
  • Alanine / pharmacology
  • Animals
  • Brain Chemistry / physiology*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cerebellum / cytology
  • Cerebellum / drug effects
  • Electrophysiology
  • Female
  • Ibotenic Acid / analogs & derivatives*
  • Ibotenic Acid / antagonists & inhibitors
  • Ibotenic Acid / pharmacology
  • In Vitro Techniques
  • Kainic Acid / antagonists & inhibitors
  • Kainic Acid / pharmacology
  • Microinjections
  • Neurons / drug effects
  • Oocytes / drug effects*
  • Pregnancy
  • Pyrimidinones
  • RNA, Messenger / administration & dosage
  • RNA, Messenger / pharmacology*
  • Rats
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Thiocyanates / pharmacology*
  • Uracil
  • Xenopus laevis
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid


  • Pyrimidinones
  • RNA, Messenger
  • Receptors, N-Methyl-D-Aspartate
  • Thiocyanates
  • willardiine
  • Ibotenic Acid
  • Uracil
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Alanine
  • Kainic Acid