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KMID : 0848120080330030117
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International Journal of Oral Biology
2008 Volume.33 No. 3 p.117 ~ p.123
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Mechanisms of tert-Buthyl Hydroperoxide-induced Membrane Depolarization in Rat Spinal Substantia Gelatinosa Neurons
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Lim Seong-Jun
Chun Sang-Woo
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Abstract
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Reactive oxygen species (ROS) are toxic agents that may be involved in various neurodegenerative diseases. Recent studies indicate that ROS can act as modulators of neuronal activity, and are critically involved in persistent pain primarily through spinal mechanisms. In the present study, whole cell patch clamp recordings were carried out to investigate the effects of tert-buthyl hydroperoxide (t-BuOOH), an ROS, on neuronal excitability and the mechanisms underlying changes of membrane excitability. In current clamp condition, application of t-BuOOH caused a reversible membrane depolarization and firing activity in substantia gelatinosa (SG) neurons. When slices were pretreated with phenyl-N-tert-buthylnitrone (PBN) and ascorbate, ROS scavengers, t-BuOOH failed to induce membrane depolarization. However, isoascorbate did not prevent t-BuOOH-induced depolarization, suggesting that the site of ROS action is intracellular. The t-BuOOH-induced depolarization was not blocked by pretreatment with dithiothreitol (DTT), a sulfhydryl-reducing agent. The membrane-impermeant thiol oxidant 5,5-dithiobis 2-nitrobenzoic acid (DTNB) failed to induce membrane depolarization, suggesting that the changes of neuronal excitability by t-BuOOH are not caused by the modification of extrathiol group. The t-BuOOH-induced depolarization was suppressed by the phospholipase C (PLC) blocker U-73122 and inositol triphosphate (IP3)receptor antagonist 2-aminoethoxydiphenylbolate (APB), and after depletion of intracellular Ca²+ pool by thapsigargin. These data suggest that ROS generated by peripheral nerve injury can induce central sensitization in spinal cord, and t-BuOOH-induced depolarization may be regulated by intracellular Ca²+ store mainly via PLC-IP₃pathway.
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KEYWORD
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tert-buthyl hydroperoxide, substantia gelatinosa, depolarization, PLC-IP₃pathway, pain
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