TY - JOUR
T1 - The effect of zinc on glycinergic inhibitory postsynaptic currents in rat spinal dorsal horn neurons
AU - Eto, Kei
AU - Arimura, Yukiko
AU - Nabekura, Junichi
AU - Noda, Mami
AU - Ishibashi, Hitoshi
N1 - Funding Information:
We thank Prof. D. A. Brown (University College London, UK) for reading the manuscript and valuable suggestions. This work was supported by Grants-in-Aid for Scientific Research of Japan Society for Promotion of Science and Research Grant in Priority Area Research of the Ministry of Education, Culture, Sports, Science and Technology, Japan.
PY - 2007/8/3
Y1 - 2007/8/3
N2 - 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 μM 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 μM, on the other hand, zinc potentiated the amplitude of spontaneous IPSCs but had no effect on the frequency. At a high concentration of 100 μM, 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 μM zinc was inhibited by blocking the voltage-dependent Ca2+ channels in the presence of both ω-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 μM 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 Ca2+ 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.
AB - 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 μM 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 μM, on the other hand, zinc potentiated the amplitude of spontaneous IPSCs but had no effect on the frequency. At a high concentration of 100 μM, 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 μM zinc was inhibited by blocking the voltage-dependent Ca2+ channels in the presence of both ω-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 μM 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 Ca2+ 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.
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U2 - 10.1016/j.brainres.2007.05.060
DO - 10.1016/j.brainres.2007.05.060
M3 - Article
C2 - 17604007
AN - SCOPUS:34447536750
VL - 1161
SP - 11
EP - 20
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1
ER -