Hydrogen peroxide increases GABAergic mIPSC through presynaptic release of calcium from IP3 receptor-sensitive stores in spinal cord substantia gelatinosa neurons.
Hydrogen peroxide increases GABAergic mIPSC through presynaptic release of calcium from IP3 receptor-sensitive stores in spinal cord substantia gelatinosa neurons.
复制标题
过氧化氢通过脊髓胶质神经元中 IP3 受体敏感储存的突触前释放钙来增加 GABA 能 mIPSC。
DOI：
10.1111/j.1460-9568.2007.05323.x
复制
发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Yang,Jay
中科院分区：
文献类型：
--
作者：
Takahashi,Ayako;Mikami,Maya;Yang,Jay
GABAergic interneurons of the spinal cord substantia gelatinosa regulate the transmission of nociceptive information. Hydrogen peroxide (H2O2) is likely a diffusible messenger contributing to the development of long‐lasting pathological pain states after nerve injury. In this study, we examined the presynaptic effects of H2O2on the inhibitory interneurons of mouse substantia gelatinosa (SG) using whole‐cell patch‐clamp recordings from spinal cord slices. H2O2increased the frequency of GABAergic miniature inhibitory postsynaptic current (mIPSC) in a concentration‐dependent (10–1000 µm) manner. The profound increase in mIPSC frequency was diminished by thapsigargin or cyclopiazonic acid suggesting that the intracellular stored pool was the source of presynaptic calcium. Further examination revealed the 2‐aminoethoxydiphenil borate blockable inositol‐(1,4,5) trisphosphate receptor (IP3R) regulated pool of stored calcium as the likely source. The phospholipase C (PLC) blocker, 1‐(6‐[([17β]‐3‐methoxyestra‐1,3,5[10]‐trien‐17‐yl)‐amino]hexyl)‐1H‐pyrrole‐2,5‐dione (U73122), did not block the frequency increase, which suggested that the site of action of H2O2lies downstream in the IP3signalling pathway, and nifedipine‐sensitivity of the frequency increase indicated a possible role of calcium‐induced calcium‐release. However, a direct examination of L‐type voltage‐gated calcium channels (VGCC) demonstrated that H2O2did not increase the calcium influx through these channels. The H2O2effect on mIPSC frequency was markedly reduced in the opisthotonus (Opt) mutant mice with a known deletion in the IP3R1 gene. We demonstrated that H2O2increased presynaptic activity in the GABAergic interneurons by the release of calcium from the IP3R‐regulated intracellular pool. The presynaptic IP3R could emerge as a novel target for preventing H2O2‐induced synaptic plasticity in substantia gelatinosa leading to pathological pain states.
