Voltage-gated potassium channel subfamily q member 4 (Kcnq4) is predominantly expressed by hair cells and auditory neurons and regulates the neuronal excitability in the auditory pathway. Although it is further detected in myelinated large-diameter dorsal root ganglia (DRG) neurons in the periphery, the expression and function of Kcnq4 channel in nociceptors remains unknown. Here we showed that Kcnq4 is substantially expressed by unmyelinated small-diameter DRG neurons in both human and mouse. In spite of a dispensable role in acute pain and chronic skin inflammation, Kcnq4 is specifically involved in the regulation of scratching behavior through controlling action potential firing properties, evidenced by the increased neuronal excitability in small-diameter DRG neurons isolated from Kcnq4 deficient mice. Moreover, genetic ablation of Kcnq4 in Trpv1-positive neurons exacerbates both acute and chronic itch behavior in mice. Taken together, our results uncover a functional role of Trpv1-lineage neuron-expressing Kcnq4 channel in the modulation of itch-specific neuronal excitation in the periphery.

中文翻译：

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Trpv1 谱系神经元表达 Kcnq4 通道调节小鼠的瘙痒感。


电压门控钾通道亚家族 q 成员 4 （Kcnq4） 主要由毛细胞和听觉神经元表达，并调节听觉通路中的神经元兴奋性。尽管在外围的有髓大直径背根神经节 （DRG） 神经元中进一步检测到它，但 Kcnq4 通道在伤害感受器中的表达和功能仍然未知。在这里，我们表明 Kcnq4 在人和小鼠中由无髓小直径 DRG 神经元基本表达。尽管在急性疼痛和慢性皮肤炎症中起着可有可无的作用，但 Kcnq4 通过控制动作电位放电特性专门参与搔抓行为的调节，从 Kcnq4 缺陷小鼠中分离的小直径 DRG 神经元中神经元兴奋性增加就证明了这一点。此外，Trpv1 阳性神经元中 Kcnq4 的基因消融加剧了小鼠的急性和慢性瘙痒行为。综上所述，我们的结果揭示了表达 Trpv1 谱系神经元的 Kcnq4 通道在调节外围瘙痒特异性神经元兴奋中的功能作用。