Intense isolectin-B4 binding in rat dorsal root ganglion neurons distinguishes C-fiber nociceptors with broad action potentials and high Nav1.9 expression
Intense isolectin-B4 binding in rat dorsal root ganglion neurons distinguishes C-fiber nociceptors with broad action potentials and high Nav1.9 expression
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DOI：
10.1523/jneurosci.1072-06.2006
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发表时间：
2006-07-05
影响因子：
5.3
通讯作者：
Lawson, Sally N.
中科院分区：
文献类型：
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作者：
Fang, Xin;Djouhri, Laiche;Lawson, Sally N.
与异凝集素 B4 (IB4) 的结合和酪氨酸激酶 A (trkA)（高亲和力 NGF 受体）的表达已被用来定义伤害性小背根神经节 (DRG) 神经元的两个不同亚组。我们之前表明只有伤害感受器具有高 trkA 水平。然而，缺乏关于单个鉴定的 IB4 结合神经元体内感觉和电生理特性及其 trkA 表达水平的信息。 IB4 阳性 (IB4+) 和小暗神经元具有相似的大小分布。我们检查了超过 120 个注射染料的 DRG 神经元中的 IB4 结合水平，并记录了体内的感觉和电生理特性。还测量了这些神经元中 trkA 和两个 TTX 抗性钠通道（Nav1.8 和 Nav1.9）的相对免疫强度。 IB4(+)神经元分为强或弱IB4(+)。所有强IB4(+)神经元均为C-伤害感受器类型(C-纤维伤害感受或无反应)。在检查的 32 个 C 伤害感受器型神经元中，大约 50% 是强 IB4(+)，大约 20% 是弱 IB4(+)，大约 30% 是 IB4(-)。 Delta 低阈值机械感受 (LTM) 神经元为弱 IB4+ 或 IB4-。检查的所有 33 个 A 纤维伤害感受器和所有 44 个 A α/β-LTM 神经元均为 IB4-。与IB4-C伤害感受器型神经元相比，IB4+对于Nav1.9（但不是Nav1.8）具有更长的体细胞动作电位持续时间和上升时间、更慢的传导速度、更多的负膜电位和更大的免疫强度。 C 神经元中 IB4 结合的免疫强度与 Nav1.9 呈正相关，但与 Nav1.8 不呈正相关。在 23 个 C 神经元中检测 trkA 和 IB4，其中 35% 为 trkA+/IB4+，但免疫强度呈负相关； 26% 为 IB4+/trkA-，35% 为 IB4-/trkA+。我们得出的结论是，IB4+ DRG 神经元完全是 C 伤害感受器类型，并且 Nav1.9 的高表达可能有助于其独特的膜特性。
Binding to isolectin-B4 (IB4) and expression of tyrosine kinase A (trkA) (the high-affinity NGF receptor) have been used to define two different subgroups of nociceptive small dorsal root ganglion (DRG) neurons. We previously showed that only nociceptors have high trkA levels. However, information about sensory and electrophysiological properties in vivo of single identified IB4-binding neurons, and about their trkA expression levels, is lacking. IB4-positive (IB4+) and small dark neurons had similar size distributions. We examined IB4-binding levels in > 120 dye-injected DRG neurons with sensory and electrophysiological properties recorded in vivo. Relative immunointensities for trkA and two TTX-resistant sodium channels (Nav1.8 and Nav1.9) were also measured in these neurons. IB4(+) neurons were classified as strongly or weakly IB4(+).All strongly IB4(+) neurons were C-nociceptor type (C-fiber nociceptive or unresponsive). Of 32 C-nociceptor-type neurons examined, similar to 50% were strongly IB4(+), similar to 20% were weakly IB4(+) and similar to 30% were IB4(-). A delta low-threshold mechanoreceptive (LTM) neurons were weakly IB4+ or IB4-. All 33 A-fiber nociceptors and all 44 A alpha/beta-LTM neurons examined were IB4-. IB4+ compared with IB4- C-nociceptor-type neurons had longer somatic action potential durations and rise times, slower conduction velocities, more negative membrane potentials, and greater immunointensities for Nav1.9 but not Nav1.8. Immunointensities of IB4 binding in C-neurons were positively correlated with those of Nav1.9 but not Nav1.8. Of 23 C-neurons tested for both trkA and IB4, similar to 35% were trkA+/IB4+ but with negatively correlated immunointensities; 26% were IB4+/trkA-, and 35% were IB4-/trkA+. We conclude that strongly IB4+ DRG neurons are exclusively C-nociceptor type and that high Nav1.9 expression may contribute to their distinct membrane properties.