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Mechanisms of tert-Buthyl Hydroperoxide-induced Membrane Depolarization in Rat Spinal Substantia Gelatinosa Neurons

천상우|임성준
대한구강생물학회 (Korean Academy Of Oral Biology)|2008.09|International Journal of Oral Biology|제33권 제3호|pp. 117-123

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주제분류치의학

초록

Abstract

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-BuOOHinduced 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 Ca ²+ store mainly via PLC-IP3 pathway.

참고문헌 (39)

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관련 논문AI추천

Effects of Hydrogen Peroxide on Neuronal Excitability and Synaptic Transmission in Rat Substantia Gelatinosa Neurons손용, 천상우대한구강생물학회 · International Journal of Oral Biology2007 · 제32권 제4호Effects of NaOCl on Neuronal Excitability and Intracellular Calcium Concentration in Rat Spinal Substantia Gelatinosa Neurons박아름, 이해인, 천상우대한구강생물학회 · International Journal of Oral Biology2013 · 제38권 제1호Reactive Oxygen Species and Nitrogen Species Differentially Regulate Neuronal Excitability in Rat Spinal Substantia Gelatinosa Neurons박아롬, 이해인, 천상우대한구강생물학회 · International Journal of Oral Biology2014 · 제39권 제4호척수 아교질 세포의 흥분성과 세포내 칼슘농도에 대한 활성산소의 영향에 대한 연구이해인, 천상우치의학연구원 · Oral Biology Research2011 · 제35권 제1호Effects of Mitochondrial Reactive Oxygen Species on Neuronal Excitability in Rat Spinal Substantia Gelatinosa Neurons박아름, 이해인, 천상우대한구강생물학회 · International Journal of Oral Biology2012 · 제37권 제1호Pre- and Postsynaptic Actions of Reactive Oxygen Species and Nitrogen Species in Spinal Substantia Gelatinosa Neurons박아름, 천상우대한구강생물학회 · International Journal of Oral Biology2018 · 제43권 제4호

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