Ostrowski T D, Hasser E M, Heesch C M, Kline D D
Department of Biomedical Sciences, Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA.
Department of Biomedical Sciences, Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA.
Neuroscience. 2014 Mar 14;262:53-69. doi: 10.1016/j.neuroscience.2013.12.055. Epub 2014 Jan 4.
Hydrogen peroxide (H₂O₂) is a stable reactive oxygen species and potent neuromodulator of cellular and synaptic activity. Centrally, endogenous H₂O₂ is elevated during bouts of hypoxia-reoxygenation, a variety of disease states, and aging. The nucleus tractus solitarii (nTS) is the central termination site of visceral afferents for homeostatic reflexes and contributes to reflex alterations during these conditions. We determined the extent to which H₂O₂ modulates synaptic and membrane properties in nTS neurons in rat brainstem slices. Stimulation of the tractus solitarii (which contains the sensory afferent fibers) evoked synaptic currents that were not altered by 10-500 μM H₂O₂. However, 500 μM H₂O₂ modulated several intrinsic membrane properties of nTS neurons, including a decrease in input resistance (R(i)), hyperpolarization of resting membrane potential (RMP) and action potential (AP) threshold (THR), and an initial reduction in AP discharge to depolarizing current. H₂O₂ increased conductance of barium-sensitive potassium currents, and block of these currents ablated H₂O₂-induced changes in RMP, Ri and AP discharge. Following washout of H₂O₂ AP discharge was enhanced due to depolarization of RMP and a partially maintained hyperpolarization of THR. Hyperexcitability persisted with repeated H₂O₂ exposure. H₂O₂ effects on RMP and THR were ablated by intracellular administration of the antioxidant catalase, which was immunohistochemically identified in neurons throughout the nTS. Thus, H₂O₂ initially reduces excitability of nTS neurons that is followed by sustained hyperexcitability, which may play a profound role in cardiorespiratory reflexes.
过氧化氢（H₂O₂）是一种稳定的活性氧物质，也是细胞和突触活动的强效神经调节剂。在中枢神经系统中，内源性H₂O₂在缺氧-复氧发作、多种疾病状态及衰老过程中会升高。孤束核（nTS）是内脏传入神经进行稳态反射的中枢终末部位，并且在这些情况下会导致反射改变。我们确定了H₂O₂对大鼠脑干切片中nTS神经元突触和膜特性的调节程度。刺激孤束（包含感觉传入纤维）诱发的突触电流不受10 - 500 μM H₂O₂的影响。然而，500 μM H₂O₂调节了nTS神经元的几种内在膜特性，包括输入电阻（R(i)）降低、静息膜电位（RMP）和动作电位（AP）阈值（THR）超极化，以及对去极化电流的AP发放最初减少。H₂O₂增加了钡敏感钾电流的电导，阻断这些电流消除了H₂O₂诱导的RMP、Ri和AP发放的变化。在冲洗掉H₂O₂后，由于RMP去极化和THR部分维持的超极化，AP发放增强。重复暴露于H₂O₂后，兴奋性持续增强。通过细胞内给予抗氧化剂过氧化氢酶可消除H₂O₂对RMP和THR的影响，过氧化氢酶在整个nTS的神经元中通过免疫组织化学鉴定。因此，H₂O₂最初降低nTS神经元的兴奋性，随后是持续的兴奋性增强，这可能在心肺反射中起重要作用。
