Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission.
Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission.
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伤害感受神经元体膜电位的控制及其对外周伤害感受传递的影响。
DOI：
10.1016/j.pain.2014.08.025
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发表时间：
2014-11
期刊：
影响因子：
7.4
通讯作者：
Gamper N
中科院分区：
文献类型：
--
作者：
Du X;Hao H;Gigout S;Huang D;Yang Y;Li L;Wang C;Sundt D;Jaffe DB;Zhang H;Gamper N
我们确定了影响痛觉感觉神经元静息膜电位的主要离子通道，并证明了这些神经元的体细胞/胞周膜电位的变化可以强烈影响外周痛觉传递。外周感觉神经节包含向中枢神经系统传递体感觉输入的传入纤维体。越来越多的证据表明，感觉神经元的躯体/周围区域可以影响外周感觉传递。静息膜电位（rest membrane potential, Erest）是调节兴奋性的重要机制，但令人惊讶的是，对于感觉神经元体中Erest是如何调节的，以及体细胞/周围Erest的变化是如何影响外周感觉传递的，我们知之甚少。我们首先评估了几种主要离子通道对培养的小直径，主要是辣椒素敏感（假定是伤害性的）背根神经节（DRG）神经元est的影响。对est的最强和最普遍的影响是通过调节M通道、K2P通道和4-氨基吡啶敏感的KV通道实现的，而超极化激活的环核苷酸门控通道、电压门控Na+通道和t型Ca2+通道也在较小程度上促进est。其次，我们通过操纵DRG内感觉神经元的离子通道，研究了不同的体细胞/体细胞周围膜电位如何影响体内外周伤害感受的传递。在体内急性局灶性应用M或KATP通道增强剂或超极化激活的环核苷酸门控通道阻滞剂对L5 DRG可显著减轻后爪注射缓激肽引起的疼痛。最后，我们通过计算模型展示了体细胞/体细胞周围超极化与DRG内t结的低通滤波特性是如何干扰动作电位传播的。我们的研究破译了一组离子通道，这些离子通道设置了伤害性神经元的躯体休息，并为外周伤害性神经元的躯体和周围区室的强大过滤作用提供了强有力的证据。
We identified major ion channels influencing the resting membrane potential of nociceptive sensory neurons and demonstrated that changes of somatic/perisomatic membrane potential of these neurons can strongly influence peripheral nociceptive transmission. Peripheral sensory ganglia contain somata of afferent fibres conveying somatosensory inputs to the central nervous system. Growing evidence suggests that the somatic/perisomatic region of sensory neurons can influence peripheral sensory transmission. Control of resting membrane potential (Erest) is an important mechanism regulating excitability, but surprisingly little is known about how Erest is regulated in sensory neuron somata or how changes in somatic/perisomatic Erest affect peripheral sensory transmission. We first evaluated the influence of several major ion channels on Erest in cultured small-diameter, mostly capsaicin-sensitive (presumed nociceptive) dorsal root ganglion (DRG) neurons. The strongest and most prevalent effect on Erest was achieved by modulating M channels, K2P and 4-aminopiridine-sensitive KV channels, while hyperpolarization-activated cyclic nucleotide-gated, voltage-gated Na+, and T-type Ca2+ channels to a lesser extent also contributed to Erest. Second, we investigated how varying somatic/perisomatic membrane potential, by manipulating ion channels of sensory neurons within the DRG, affected peripheral nociceptive transmission in vivo. Acute focal application of M or KATP channel enhancers or a hyperpolarization-activated cyclic nucleotide-gated channel blocker to L5 DRG in vivo significantly alleviated pain induced by hind paw injection of bradykinin. Finally, we show with computational modelling how somatic/perisomatic hyperpolarization, in concert with the low-pass filtering properties of the t-junction within the DRG, can interfere with action potential propagation. Our study deciphers a complement of ion channels that sets the somatic Erest of nociceptive neurons and provides strong evidence for a robust filtering role of the somatic and perisomatic compartments of peripheral nociceptive neuron.
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影响因子：
5.3
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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