The effect of zinc on glycinergic spontaneous inhibitory postsynaptic currents (IPSCs) was investigated using the whole-cell patch-clamp technique in mechanically dissociated rat spinal dorsal horn neurons. Zinc at a concentration of 10 microM reversibly increased the spontaneous IPSC frequency without changing the current amplitudes, suggesting that zinc increases spontaneous glycine release from presynaptic nerve terminals. At a low concentration of 1 microM, on the other hand, zinc potentiated the amplitude of spontaneous IPSCs but had no effect on the frequency. At a high concentration of 100 microM, zinc increased the spontaneous IPSC frequency while it inhibited the IPSC amplitude. The current evoked by exogenously applied glycine was potentiated and inhibited by low and high concentrations of zinc, respectively. The increase in spontaneous IPSC frequency by 10 microM zinc was inhibited by blocking the voltage-dependent Ca(2+) channels in the presence of both omega-conotoxin-MVIIC and nifedipine. The facilitatory effect of zinc on spontaneous IPSC frequency was also inhibited in the presence of tetrodotoxin. In the slice preparation, 30 microM zinc potentiated the evoked IPSC amplitude and decreased the paired pulse ratio. These results suggest that, in addition to an action on the postsynaptic glycine receptors, zinc may depolarize the presynaptic nerve terminals, leading to an activation of voltage-dependent Na(+) and Ca(2+) channels that in turn increases glycine release. Since dorsal horn neurons receive nociceptive inputs, zinc may play an important role in the regulation of sensory transmission.