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

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. 1993 British Pharmacological Society