Thiocyanate ions selectively antagonize AMPA-evoked responses in Xenopus laevis oocytes microinjected with rat brain mRNA.
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.
Bowie
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School of Pharmacy, Department of Pharmacology, Brunswick Square, London.
Smart
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D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D004594:Electrophysiology; D005260:Female; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008845:Microinjections; D009474:Neurons / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects*; D011247:Pregnancy; D011744:Pyrimidinones; D012333:RNA, Messenger / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects; D013861:Thiocyanates / Q000494:pharmacology*; D014498:Uracil; D014982:Xenopus laevis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D011744:Pyrimidinones; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D013861:Thiocyanates; C002872:willardiine; D007051:Ibotenic Acid; D014498:Uracil; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000409:Alanine; D007608:Kainic Acid