The Low-Threshold Calcium Channel Cav3.2 Determines Low-Threshold Mechanoreceptor Function
The Low-Threshold Calcium Channel Cav3.2 Determines Low-Threshold Mechanoreceptor Function
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DOI：
10.1016/j.celrep.2014.12.042
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发表时间：
2015-01-20
期刊：
影响因子：
8.8
通讯作者：
Bourinet, Emmanuel
中科院分区：
文献类型：
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作者：
Francois, Amaury;Schueetter, Niklas;Bourinet, Emmanuel
t型钙通道Cav3.2是感觉功能的关键调节因子，但其在初级传入神经元中的表达模式及其对模式特异性信号的贡献尚不清楚。在这里，我们使用一种独特的敲入/flox小鼠品系来阐明这一问题，其中Cav3.2被Cav3.2-表面-黄道GFP融合所取代。我们证明Cav3.2是两种主要的低阈机械感受器（LTMRs）的选择性标记物，a delta-和C-LTMRs，支配着最丰富的皮肤毛囊。Cav3.2沿着ltmr -纤维轨迹的存在与多个位点的关键作用一致，这使得它们具有很强的兴奋性。引人注目的是，c - ltmr特异性敲除揭示了Cav3.2调节轻触感知和有害的机械冷和化学感觉，并且对于建立削弱神经性疼痛的异动症状至关重要，这一机制被认为完全是a - ltmr特异性的。总的来说，我们的研究结果支持Cav3.2在触摸/疼痛病理生理中的基本作用，验证了它们与缓解机械和冷异常性痛的重要药理相关性。
The T-type calcium channel Cav3.2 emerges as a key regulator of sensory functions, but its expression pattern within primary afferent neurons and its contribution to modality-specific signaling remain obscure. Here, we elucidate this issue using a unique knockin/flox mouse strain wherein Cav3.2 is replaced by a functional Cav3.2-surface-ecliptic GFP fusion. We demonstrate that Cav3.2 is a selective marker of two major low-threshold mechanoreceptors (LTMRs), A delta- and C-LTMRs, innervating the most abundant skin hair follicles. The presence of Cav3.2 along LTMR-fiber trajectories is consistent with critical roles at multiple sites, setting their strong excitability. Strikingly, the C-LTMR-specific knockout uncovers that Cav3.2 regulates light-touch perception and noxious mechanical cold and chemical sensations and is essential to build up that debilitates allodynic symptoms of neuropathic pain, a mechanism thought to be entirely A-LTMR specific. Collectively, our findings support a fundamental role for Cav3.2 in touch/pain pathophysiology, validating their critic pharmacological relevance to relieve mechanical and cold allodynia.