Rocha-Sanchez Sonia M S, Morris Kenneth A, Kachar Bechara, Nichols David, Fritzsch Bernd, Beisel Kirk W
Department of Oral Biology, Creighton University School of Dentistry, 2500 California Plaza, Omaha, NE 68178, USA.
Brain Res. 2007 Mar 30;1139:117-25. doi: 10.1016/j.brainres.2006.12.087. Epub 2007 Jan 8.
Sensory signal transduction of the inner ear afferent neurons and hair cells (HCs) requires numerous ionic conductances. The KCNQ4 voltage-gated M-type potassium channel is thought to set the resting membrane potential in cochlear HCs. Here we describe the spatiotemporal expression patterns of Kcnq4 and the associated alternative splice forms in the HCs of vestibular labyrinth. Whole mount immunodetection, qualitative and quantitative RT-PCR were performed to characterize the expression patterns of Kcnq4 transcripts and proteins. A topographical expression and upregulation of Kcnq4 during development was observed and indicated that Kcnq4 is not restricted to either a specific vestibular structure or cell type, but is present in afferent calyxes, vestibular ganglion neurons, and both type I and type II HCs. Of the four alternative splice variants, Kcnq4_v1 transcripts were the predominant form in the HCs, while Kcnq4_v3 was the major variant in the vestibular neurons. Differential quantitative expression of Kcnq4_v1 and Kcnq4_v3 were respectively detected in the striolar and extra-striolar regions of the utricle and saccule. Analysis of gerbils and rats yielded results similar to those obtained in mice, suggesting that the spatiotemporal expression pattern of Kcnq4 in the vestibular system is conserved among rodents. Analyses of vestibular HCs of Bdnf conditional mutant mice, which are devoid of any innervation, demonstrate that regulation of Kcnq4 expression in vestibular HCs is independent of innervation.
内耳传入神经元和毛细胞(HCs)的感觉信号转导需要多种离子电导。KCNQ4电压门控M型钾通道被认为可设定耳蜗毛细胞的静息膜电位。在此,我们描述了Kcnq4在前庭迷路毛细胞中的时空表达模式以及相关的可变剪接形式。采用全组织免疫检测、定性和定量逆转录-聚合酶链反应来表征Kcnq4转录本和蛋白质的表达模式。观察到Kcnq4在发育过程中的拓扑表达和上调,这表明Kcnq4并不局限于特定的前庭结构或细胞类型,而是存在于传入花萼、前庭神经节神经元以及I型和II型毛细胞中。在四种可变剪接变体中,Kcnq4_v1转录本是毛细胞中的主要形式,而Kcnq4_v3是前庭神经元中的主要变体。在椭圆囊和球囊的纹状区和纹状外区分别检测到Kcnq4_v1和Kcnq4_v3的差异定量表达。对沙鼠和大鼠的分析结果与在小鼠中获得的结果相似,这表明Kcnq4在前庭系统中的时空表达模式在啮齿动物中是保守的。对缺乏任何神经支配的Bdnf条件突变小鼠的前庭毛细胞进行分析表明,前庭毛细胞中Kcnq4表达的调节与神经支配无关。