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

It was demonstrated in our recent study that Zn(2+) had dual effects on Ca(2+)-permeable AMPA receptors on carp retinal horizontal cells. However, the possible mechanism(s) underlying the Zn(2+) effects is still unclear. In the present study, we examined the Zn(2+) 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 Zn(2+) (10 microM) exerted on the amplitude of the current mediated by Ca(2+)-permeable AMPA receptors was more remarkable in the presence of moderate concentration of CTZ (20 microM). Meanwhile, the inhibitory effect induced by high concentration Zn(2+) (1 mM) was not affected by CTZ. Furthermore, the involvement of extracellular Ca(2+) in the Zn(2+) effects was also examined. It was shown that the inhibitory effect induced by high concentration Zn(2+) (1 mM) was abolished or significantly attenuated in Ca(2+)-free (0 mM) Ringer's, but significantly enhanced in high-Ca(2+) (20 mM) Ringer's. However, the Zn(2+) (10 microM) potentiation effect was not changed either in Ca(2+)-free (0 mM) or high-Ca(2+) (20 mM) Ringer's. These results suggest that the Zn(2+) potentiation effect involves the interaction with CTZ-binding site on the AMPA receptors, while the Zn(2+) inhibitory effect is related to the extracellular Ca(2+) concentration. Overall, the dual effects that Zn(2+) exerts on Ca(2+)-permeable AMPA receptors on retinal horizontal cells are mediated by separate mechanisms.