TRPC1 contributes to light-touch sensation and mechanical responses in low-threshold cutaneous sensory neurons
TRPC1 contributes to light-touch sensation and mechanical responses in low-threshold cutaneous sensory neurons
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DOI：
10.1152/jn.00658.2011
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发表时间：
2012-02-01
影响因子：
2.5
通讯作者：
Stucky, Cheryl L.
中科院分区：
文献类型：
--
作者：
Garrison, Sheldon R.;Dietrich, Alexander;Stucky, Cheryl L.
Garrison SR，Dietrich A，Stucky CL. TRPC 1参与低阈值皮肤感觉神经元的轻触感觉和机械反应。J Neurophysiol 107：913-922，2012.首次发表于2011年11月9日; doi：10.1152/jn.00658.2011.-在哺乳动物系统中，构成机械感觉基础的细胞蛋白在很大程度上仍然是个谜。机械敏感的离子通道被认为可以区分皮肤中的压力、拉伸和其他类型的触觉信号。瞬时受体电位经典1（TRPC 1）是一个候选的机械敏感通道，在初级传入感觉神经元中表达。然而，其在这些神经元的机械敏感性中的作用尚不清楚。在这里，我们调查TRPC 1依赖的反应，无害和有害的机械力。使用离体皮肤-神经制备物从隐神经记录皮肤有髓A-纤维和无髓C-纤维神经元中的机械诱发动作电位，所述隐神经终止于后爪的背侧有毛皮肤。我们的数据显示，在TRPC 1缺陷小鼠中，与野生型对照组相比，在缓慢适应的A β纤维（主要支配默克尔细胞）和快速适应的A δ绒毛传入纤维中，机械诱发的动作电位降低了近50%。相比之下，在缓慢适应A β-机械受体或无髓鞘C-纤维中没有发现差异，它们主要对伤害性刺激作出反应。这些结果表明，TRPC 1可能是重要的检测无害的机械力。我们同时研究了TRPC 1在足底后爪皮肤机械力行为反应中的作用。对于无害的刺激，我们开发了一种新的使用“膨化”棉签的轻中风测定。此外，我们使用了重复的光，大概是无害的点状刺激与低阈值冯弗雷细丝（0.68 mN）。与我们的光触摸传入的电生理数据一致，TRPC 1缺陷小鼠与野生型对照相比，在对光中风和光点状机械测定的行为反应中表现出近50%的下降。相比之下，TRPC 1缺陷小鼠表现出正常的缩爪反应，更强烈的机械刺激，通常被认为是伤害性行为的措施。
Garrison SR, Dietrich A, Stucky CL. TRPC1 contributes to light-touch sensation and mechanical responses in low-threshold cutaneous sensory neurons. J Neurophysiol 107: 913-922, 2012. First published November 9, 2011; doi:10.1152/jn.00658.2011.-The cellular proteins that underlie mechanosensation remain largely enigmatic in mammalian systems. Mechanically sensitive ion channels are thought to distinguish pressure, stretch, and other types of tactile signals in skin. Transient receptor potential canonical 1 (TRPC1) is a candidate mechanically sensitive channel that is expressed in primary afferent sensory neurons. However, its role in the mechanical sensitivity of these neurons is unclear. Here, we investigated TRPC1-dependent responses to both innocuous and noxious mechanical force. Mechanically evoked action potentials in cutaneous myelinated A-fiber and unmyelinated C-fiber neurons were quantified using the ex vivo skin-nerve preparation to record from the saphenous nerve, which terminates in the dorsal hairy skin of the hindpaw. Our data reveal that in TRPC1-deficient mice, mechanically evoked action potentials were decreased by nearly 50% in slowly adapting A beta-fibers, which largely innervate Merkel cells, and in rapidly adapting A delta-Down-hair afferent fibers compared with wild-type controls. In contrast, differences were not found in slowly adapting A beta-mechano-receptors or unmyelinated C-fibers, which primarily respond to nociceptive stimuli. These results suggest that TRPC1 may be important in the detection of innocuous mechanical force. We concurrently investigated the role of TRPC1 in behavioral responses to mechanical force to the plantar hindpaw skin. For innocuous stimuli, we developed a novel light stroke assay using a "puffed out" cotton swab. Additionally, we used repeated light, presumably innocuous punctate stimuli with a low threshold von Frey filament (0.68 mN). In agreement with our electrophysiological data in light-touch afferents, TRPC1-deficient mice exhibited nearly a 50% decrease in behavioral responses to both the light-stroke and light punctate mechanical assays when compared with wild-type controls. In contrast, TRPC1-deficient mice exhibited normal paw withdrawal response to more intense mechanical stimuli that are typically considered measures of nociceptive behavior.