Martin Hannah R, Verdone Brandie Morris, López-Ramírez Omar, Green Merrill, Silvian Dana, Scott Emily, Cullen Kathleen E, Eatock Ruth Anne
University of Chicago, Department of Neurobiology.
Johns Hopkins University, Department of Biomedical Engineering.
bioRxiv. 2025 Jan 28:2025.01.28.634388. doi: 10.1101/2025.01.28.634388.
Vestibular hair cells (HCs) faithfully and rapidly detect head motions and gravity, driving motor reflexes that stabilize balance and gaze during locomotion. With the transition from water to land, the amniote vestibular inner ear added type I HCs, which differ from amniote type II HCs and anamniote HCs by their large calyx afferent synapse, non-quantal afferent transmission, and a large, low-voltage-activated K conductance (g). We recently showed that both g and the major type II K conductances (A-type and delayed rectifier) require K1.8 () subunits. Here we compared K1.8-null ( ) and control animals to see how K1.8 affects function as measured by receptor potentials and nonquantal postsynaptic potentials evoked by direct hair bundle motions, and by vestibulomotor behaviors. Recordings were taken from extrastriolar zones of the utricle. In both HC types, K1.8 affected receptor potentials by reducing response time and gain, increasing dampening, and expanding the frequency bandwidth toward high frequencies. Effects are most prominent in type I HCs: lowpass corner frequencies of receptor potentials in HCs of both types were ~20 Hz, . ~400 Hz in control type I and ~70 Hz in control type II. We recorded nonquantal postsynaptic potentials from extrastriolar calyces, and found that the synaptic transfer function had lower gain and greater phase lag in mice. In behavioral tests, mice had vestibular-ocular reflexes with different response dynamics at low frequencies, impaired performance on a narrow balance beam, abnormal body posture and abnormal head motions in water and on land, and also rarely assumed bipedal stances. These vestibulomotor deficits in mice likely reflect the changes noted in HCs, where K1.8 expression is concentrated; that is, slower signaling of high-frequency head motions by HCs fails to fully stabilize body and head position during locomotion. Thus, g (K1.8) contributes to fast signal transmission in the amniote vestibular inner ear and supports improved performance on challenging vestibulomotor tasks.
前庭毛细胞（HCs）能准确且迅速地检测头部运动和重力，驱动运动反射，在运动过程中稳定平衡和注视。随着从水生到陆生的转变，羊膜动物的前庭内耳增加了I型毛细胞，其与羊膜动物的II型毛细胞和无羊膜动物的毛细胞不同，具有大的花萼传入突触、非量子化传入传递以及大的、低电压激活的钾离子电导（g）。我们最近发现，g以及主要的II型钾离子电导（A型和延迟整流型）都需要K1.8（）亚基。在此，我们比较了K1.8基因敲除（）小鼠和对照动物，以观察K1.8如何影响通过受体电位以及由直接毛束运动诱发的非量子化突触后电位，以及前庭运动行为所测量的功能。记录取自椭圆囊的纹外区。在两种类型的毛细胞中，K1.8通过缩短响应时间和增益、增加阻尼以及向高频扩展频率带宽来影响受体电位。这些效应在I型毛细胞中最为显著：两种类型的毛细胞中，受体电位的低通截止频率在约为20 Hz，对照I型约为400 Hz，对照II型约为70 Hz。我们从纹外花萼记录了非量子化突触后电位，发现突触传递函数在小鼠中增益较低且相位滞后更大。在行为测试中，小鼠在低频时前庭眼反射具有不同的响应动力学，在狭窄平衡木上的表现受损，在水中和陆地上身体姿势异常且头部运动异常，并且很少采取双足站立姿势。小鼠的这些前庭运动缺陷可能反映了在毛细胞中观察到的变化，其中K1.8表达集中；也就是说，毛细胞对高频头部运动的信号传递较慢，在运动过程中无法充分稳定身体和头部位置。因此，g（K1.8）有助于羊膜动物前庭内耳中的快速信号传递，并支持在具有挑战性的前庭运动任务中提高表现。
