Nitric oxide synthase inhibitors enhance mechanosensitive Ca2+ influx in cultured dorsal root ganglion neurons
Nitric oxide synthase inhibitors enhance mechanosensitive Ca2+ influx in cultured dorsal root ganglion neurons
复制标题
DOI：
10.1016/s0006-8993(01)02407-6
复制
发表时间：
2001-06-08
期刊：
影响因子：
2.9
通讯作者：
Mayer, EA
中科院分区：
文献类型：
--
作者：
Chaban, VV;McRoberts, JA;Mayer, EA
一氧化氮（NO）可对外周感觉神经元的敏感性产生相反的影响，这取决于NO的浓度和来源以及实验设置。本研究的目的是确定内源性NO的产生在背根神经节（DRG）神经元的机械敏感性Ca 2+内流的调节中的作用。成年小鼠DRG神经元在原代培养物中生长2-5天，加载Fura-2，并通过荧光比率成像测试机械介导的[Ca 2 +]变化。在NOS抑制剂L-NAME，TRIM，或7-NI的存在下，但不是无活性的类似物U-NAME，峰值[Ca 2 +]，瞬变机械刺激增加超过2倍。无论是La 3+（25 μ M），电压激活的Ca 2+通道的抑制剂，或河豚毒素（TTX，1 μ M），电压门控Naf通道的选择性抑制剂，有机械激活[Ca 2 +]，在控制条件下的瞬变的影响。而在L-NAME存在下，La ~（3+）和TTX均部分阻断[Ca ~（2+）]_i反应。添加Gd 3+，一种机械敏感阳离子通道和L-型Ca 2+通道的阻断剂，在一定浓度（100 μ M）下，在对照条件下显著抑制机械反应，在L-NAME存在下仅部分抑制反应。La ~（3+）或TTX与Gd ~（3+）的组合几乎完全抑制了机械刺激的[Ca ~（2+）]_i瞬变。名字我们的结论是，局灶性机械刺激DRG神经元导致Ca 2+内流发生主要是通过机械敏感阳离子通道在控制条件下。在NOS抑制剂的存在下，通过电压敏感性Ca 2+通道发生额外的Ca 2+内流。这些结果表明，在培养的DRG神经元内源性产生的NO通过抑制电压门控Na+和Ca ~（2+）通道降低机械敏感性。(C)2001 Elsevier Science B. V.保留所有权利。
Nitric oxide (NO) can have opposite effects on peripheral sensory neuron sensitivity depending on the concentration and source of NO, and the experimental setting. The aim of this study was to determine the role of endogenous NO production in the regulation of mechanosensitive Ca2+ influx of dorsal root ganglion (DRG) neurons. Adult mouse DRG neurons were grown in primary culture for 2-5 days, loaded with Fura-2, and tested for mechanically mediated changes in [Ca2+], by fluorescent ratio imaging. In the presence of the NOS inhibitors L-NAME, TRIM, or 7-NI, but not the inactive analogue U-NAME, peak [Ca2+], transients to mechanical stimulation were increased more than 2-fold. Neither La3+ (25 muM), an inhibitor of voltage activated Ca2+ channels, or tetrodotoxin (TTX, 1 muM), a selective inhibitor of voltage-gated Naf channels, had an effect on mechanically activated [Ca2+], transients under control conditions. However, in the presence of L-NAME, both La3+ and TTX partially blocked the [Ca2+], response. Addition of Gd3+, a blocker of mechanosensitive cation channels and L-type Ca2+ channels, at a concentration (100 muM) that markedly inhibited the mechanical response under control conditions, only partially inhibited the response in the presence of L-NAME. The combination of either La3+ or TTX with Gd3+ caused near complete inhibition of mechanically stimulated [Ca2+], transients in the presence of l.-NAME. We conclude that focal mechanical stimulation of DRG neurons causes Ca2+ influx occurs primarily through mechanosensitive cation channels under control conditions. In the presence of NOS inhibitors, additional Ca2+ influx occurs, through voltage-sensitive Ca2+ channels. These results suggest that endogenously produced NO in cultured DRG neurons decreases mechanosensitivity by inhibiting voltage-gated Na+ and Ca2+ channels. (C) 2001 Elsevier Science B.V. All rights reserved.