Electrophysiological properties of vestibular hair cells isolated from human crista.

IF 2.8 3区 医学 Q2 CLINICAL NEUROLOGY Frontiers in Neurology Pub Date : 2025-01-22 eCollection Date: 2024-01-01 DOI:10.3389/fneur.2024.1501914
Nesrien Mohamed, Mohammad Al-Amin, Frances L Meredith, Olivia Kalmanson, Anna Dondzillo, Stephen Cass, Samuel Gubbels, Katherine J Rennie
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Abstract

Introduction: The vast majority of cellular studies on mammalian vestibular hair cells have been carried out in rodent models due in part to the inaccessibility of human inner ear organs and reports describing electrophysiological recordings from human inner ear sensory hair cells are scarce. Here, we obtained freshly harvested vestibular neuroepithelia from adult translabyrinthine surgical patients to obtain electrophysiological recordings from human hair cells.

Methods: Whole cell patch clamp recordings were performed on hair cells mechanically isolated from human cristae to characterize voltage-dependent and pharmacological properties of membrane currents. Hair cells were classified as type I or type II according to morphological characteristics and/or their electrophysiological properties.

Results: Type I hair cells exhibited low voltage-activated K+ currents (IKLV) at membrane potentials around the mean resting membrane potential (-63 mV) and large slowly activating outward K+ currents in response to depolarizing voltage steps. Recordings from type II hair cells revealed delayed rectifier type outward K+ currents that activated above the average resting potential of -55 mV and often showed some inactivation at more depolarized potentials. Perfusion with the K+ channel blocker 4-aminopyridine (1 mM) substantially reduced outward current in both hair cell types. Additionally, extracellular application of 8-bromo-cGMP inhibited IKLV in human crista type I hair cells suggesting modulation via a nitric oxide/cGMP mechanism. A slow hyperpolarization-activated current (Ih) was observed in some hair cells in response to membrane hyperpolarization below -100 mV.

Discussion: In summary, whole cell recordings from isolated human hair cells revealed ionic currents that strongly resemble mature current phenotypes previously described in hair cells from rodent vestibular epithelia. Rapid access to surgically obtained adult human vestibular neuroepithelia allows translational studies crucial for improved understanding of human peripheral vestibular function.

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人前庭毛细胞的电生理特性。
绝大多数关于哺乳动物前庭毛细胞的细胞研究都是在啮齿动物模型中进行的,部分原因是人类内耳器官难以获得,描述人类内耳感觉毛细胞电生理记录的报告很少。在这里,我们从成人迷路手术患者身上获得新鲜收获的前庭神经上皮,以获得人毛细胞的电生理记录。方法:对机械分离的人嵴毛细胞进行膜片钳全细胞记录,表征膜电流的电压依赖性和药理学性质。根据毛细胞的形态特征和/或电生理特性,将毛细胞分为I型和II型。结果:I型毛细胞在平均静息膜电位(-63 mV)附近的膜电位处表现出低电压激活的K+电流(IKLV),在去极化电压步骤下表现出大的缓慢激活的向外K+电流。II型毛细胞的记录显示,延迟整流型向外K+电流在- 55mv的平均静息电位以上激活,并且在更多的去极化电位下经常表现出一些失活。灌注K+通道阻滞剂4-氨基吡啶(1mm)可显著降低两种毛细胞类型的外向电流。此外,细胞外应用8-溴-cGMP可抑制人crisa I型毛细胞中的IKLV,这表明通过一氧化氮/cGMP机制进行调节。在-100 mV以下,一些毛细胞对膜超极化有缓慢的超极化激活电流(Ih)。讨论:总之,从分离的人类毛细胞的全细胞记录显示,离子电流与先前在啮齿动物前庭上皮毛细胞中描述的成熟电流表型非常相似。快速获得手术获得的成人前庭神经上皮细胞可以进行翻译研究,这对于提高对人类前庭外周功能的理解至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Frontiers in Neurology
Frontiers in Neurology CLINICAL NEUROLOGYNEUROSCIENCES -NEUROSCIENCES
CiteScore
4.90
自引率
8.80%
发文量
2792
审稿时长
14 weeks
期刊介绍: The section Stroke aims to quickly and accurately publish important experimental, translational and clinical studies, and reviews that contribute to the knowledge of stroke, its causes, manifestations, diagnosis, and management.
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