The mechanisms of Zn2+ effects on Ca2+-permeable AMPA receptors on carp retinal horizontal cells

It was demonstrated in our recent study that Zn2+ had dual effects on Ca2+-permeable AMPA receptors on carp retinal horizontal cells. However, the possible mechanism(s) underlying the Zn2+ effects is still unclear. In the present study, we examined the Zn2+ effects in the presence of cyclothiazide (CTZ), an allosteric potentiator of AMPA receptors, which could attenuate the receptor desensitization. It was shown that the potentiation effect that low concentration Zn2+ (10 µM) exerted on the amplitude of the current mediated by Ca2+-permeable AMPA receptors was more remarkable in the presence of moderate concentration of CTZ (20 µM). Meanwhile, the inhibitory effect induced by high concentration Zn2+ (1 mM) was not affected by CTZ. Furthermore, the involvement of extracellular Ca2+ in the Zn2+ effects was also examined. It was shown that the inhibitory effect induced by high concentration Zn2+ (1 mM) was abolished or significantly attenuated in Ca2+-free (0 mM) Ringer's, but significantly enhanced in high-Ca2+ (20 mM) Ringer's. However, the Zn2+ (10 µM) potentiation effect was not changed either in Ca2+-free (0 mM) or high-Ca2+ (20 mM) Ringer's. These results suggest that the Zn2+ potentiation effect involves the interaction with CTZ-binding site on the AMPA receptors, while the Zn2+ inhibitory effect is related to the extracellular Ca2+ concentration. Overall, the dual effects that Zn2+ exerts on Ca2+-permeable AMPA receptors on retinal horizontal cells are mediated by separate mechanisms.