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

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