NGF-induced hyperexcitability causes spontaneous fluctuations of intracellular Ca2+ in rat nociceptive dorsal root ganglion neurons
NGF-induced hyperexcitability causes spontaneous fluctuations of intracellular Ca2+ in rat nociceptive dorsal root ganglion neurons
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DOI：
10.1016/j.ceca.2008.10.002
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发表时间：
2009-03-01
期刊：
影响因子：
4
通讯作者：
Shibuya, Izumi
中科院分区：
文献类型：
--
作者：
Ozaki, Yui;Kitamura, Naoki;Shibuya, Izumi
神经生长因子是神经损伤和炎症后神经病理性疼痛的致病介质的候选者。已有报道，在100 ng/ml的NGF存在下培养的成年大鼠背根神经节（DRG）神经元产生自发动作电位。然而，目前还不清楚什么类型的DRG神经元亚群受到NGF的影响，以及这些神经元中细胞内Ca 2+浓度（[Ca 2 +]（i））如何变化。为了阐明这些观点，我们测量了在有或没有NGF的情况下培养的成年大鼠DRG神经元中的[Ca 2 +]（i）。[Ca2+]（i）在没有任何刺激的情况下，在经NGF处理的神经元亚群中自发波动，但在所有未经NGF处理的神经元中未观察到这种波动。细胞外Na+浓度、TTX和利多卡因的降低可抑制NGF诱导的[Ca 2 +]（i）波动，提示自发动作电位引起[Ca 2 +]（i）波动。神经生长因子诱导的[Ca ~（2+）]（i）波动在小型和中型神经元和辣椒素敏感神经元中比在辣椒素非反应神经元中更频繁地观察到。这些结果表明，NGF作用于伤害感受神经元，使其产生自发性动作电位和自发性[Ca ~（2+）]（i）波动。NGF引起的[Ca ~（2+）]（i）波动可能在伤害性感觉神经元膜兴奋性和神经病理性痛的调节中起一定作用。(c)2008爱思唯尔有限公司版权所有。
NGF is a candidate for a pathogenic mediator of neuropathic pain after nerve injury and inflammation. It has been reported that adult rat dorsal root ganglion (DRG) neurons cultured in the presence of NGF at 100 ng/ml generate spontaneous action potentials. However, it is unclear what types of subpopulation of DRG neurons are affected by NGF and how the intracellular Ca2+ concentration ([Ca2+](i)) changes in such neurons. To elucidate these points, we measured [Ca2+](i) in adult rat DRG neurons cultured with or without NGF. [Ca2+](i) fluctuated spontaneously in the absence of any stimuli in subpopulations of NGF-treated neurons, but such fluctuations were not observed in all NGF-untreated neurons. NGF-induced [Ca2+](i) fluctuations were inhibited by decreases in extracellular Na+ concentration, TTX and Lidocaine, suggesting that spontaneous action potentials provoked the [Ca2+](i) fluctuation. NGF-induced [Ca2+](i) fluctuation was observed in small and medium sized neurons and in Capsaicin-sensitive neurons more frequently than in Capsaicin-non-responsive neurons. These results suggest that NGF acted on the nociceptive neurons and made them hyperexcitable to generate spontaneous action potentials and spontaneous [Ca2+](i), fluctuations. The [Ca2+](i) fluctuation induced by NGF may play some role in the regulation of membrane excitability of nociceptive sensory neurons and neuropathic pain. (c) 2008 Elsevier Ltd. All rights reserved.