Zinc Modulation of Hemi-Gap-Junction Channel Currents in Retinal Horizontal Cells

Abstract

Hemi-gap-junction (HGJ) channels of retinal horizontal cells (HCs) function as transmembrane ion channels that are modulated by voltage and calcium. As an endogenous retinal neuromodulator, zinc, which is coreleased with glutamate at photoreceptor synapses, plays an important role in shaping visual signals by acting on postsynaptic HCs in vivo. To understand more fully the regulation and function of HC HGJ channels, we examined the effect of Zn2+on HGJ channel currents in bass retinal HCs. Hemichannel currents elicited by depolarization in Ca2+-free medium and in 1 mM Ca2+medium were significantly inhibited by extracellular Zn2+. The inhibition by Zn2+of hemichannel currents was dose dependent with a half-maximum inhibitory concentration of 37 μM. Compared with other divalent cations, Zn2+exhibited higher inhibitory potency, with the order being Zn2+> Cd2+≈ Co2+> Ca2+> Ba2+> Mg2+. Zn2+and Ca2+were found to modulate HGJ channels independently in additivity experiments. Modification of histidine residues with N-bromosuccinimide suppressed the inhibitory action of Zn2+, whereas modification of cysteine residues had no significant effect on Zn2+inhibition. Taken together, these results suggest that zinc acts on HGJ channels in a calcium-independent way and that histidine residues on the extracellular domain of HGJ channels mediate the inhibitory action of zinc.