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

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Abstract
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. Thiocyanate (SCN−; 50 μm − 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. 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. The response to a high concentration of AMPA (100–200 μm) 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 μm). 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. 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. 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.