Zinc modulates primary afferent fiber-evoked responses of ventral roots in neonatal rat spinal cord in vitro

Zinc ions (Zn2+) are known to modulate the functions of a variety of channels, receptors and transporters. We examined the effects of Zn2+ on the reflex potentials evoked by electrical stimulation and responses to depolarizing agents in the isolated spinal cord of the neonatal rat in vitro. Zn2+ at low concentrations (0.5–2μM) inhibited, but at high concentrations (5 and 10μM) augmented, a slow depolarizing component (slow ventral root potential). Zn2+ had no effect on fast components (monosynaptic reflex potential; fast polysynaptic reflex potential). Unlike Zn2+, strychnine (5μM), a glycine receptor antagonist, and (S),9(R)-(−)-bicuculline methobromide (10μM), a GABAA receptor antagonist, potentiated both fast polysynaptic reflex potential and slow ventral root potential. Zn2+ (5μM) did not affect depolarizing responses to glutamate and N-methyl-d-aspartate. Zn2+ enhanced the substance P-evoked depolarization in the absence of tetrodotoxin (0.3μM) but not in its presence. The dorsal root potential was inhibited by (S),9(R)-(−)-bicuculline methobromide (10μM) but not by Zn2+ (5μM). The Zn2+-potentiated slow ventral root potential was inhibited by the N-methyl-d-aspartate receptor antagonists, ketamine (10μM) and dl-2-amino-5-phosphaonovaleric acid (50μM) but not by P2X receptor antagonists, pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid (30μM) and 2′,3′-O-(2,4,6-trinitrophenyl)ATP (10μM). Ketamine (10μM) and dl-2-amino-5-phosphaonovaleric acid (50μM) almost abolished spontaneous activities increased by Zn2+. It is concluded that Zn2+ potentiated slow ventral root potential induced by primary afferent stimulation, which was mediated by the activation of N-methyl-d-aspartate receptors but not by activation of P2X receptors or blockade of glycinergic and GABAergic inhibition. Zn2+ does not seem to directly affect N-methyl-d-aspartate receptors. The release of glutamate from interneurons may play an important role in Zn2+-induced potentiation of slow ventral root potential in the spinal cord of the neonatal rat.