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Thiocyanate ions selectively antagonize AMPA‐evoked responses in Xenopus laevis oocytes microinjected with rat brain mRNA
Author(s) -
Bowie Derek,
Smart Trevor G.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13642.x
Subject(s) - ampa receptor , xenopus , kainate receptor , nmda receptor , glutamate receptor , patch clamp , chemistry , biology , voltage clamp , receptor , ionotropic effect , biophysics , medicine , microbiology and biotechnology , endocrinology , membrane potential , biochemistry , gene
1 Responses to kainate (KA), willardiine and α‐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 μ m − 4 m m ) 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 IC 50 of 1 m m . The antagonism was not dependent on the AMPA concentration. 4 The response to a high concentration of AMPA (100–200 μ m ) 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 μ m ). 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.