Department of Otolaryngology, University of Colorado School of Medicine, Aurora, Colorado.
Department of Physiology & Biophysics, University of Colorado School of Medicine, Aurora, Colorado.
J Neurophysiol. 2020 Aug 1;124(2):510-524. doi: 10.1152/jn.00124.2020. Epub 2020 Jul 15.
Vestibular afferent neurons convey information from hair cells in the peripheral vestibular end organs to central nuclei. Primary vestibular afferent neurons can fire action potentials at high rates and afferent firing patterns vary with the position of nerve terminal endings in vestibular neuroepithelia. Terminals contact hair cells as small bouton or large calyx endings. To investigate the role of Na currents () in firing mechanisms, we investigated biophysical properties of in calyx-bearing afferents. Whole cell patch-clamp recordings were made from calyx terminals in thin slices of gerbil crista at different postnatal ages: immature [postnatal day (P)5-P8, young (P13-P15), and mature (P30-P45)]. A large transient Na current () was completely blocked by 300 nM tetrodotoxin (TTX) in mature calyces. In addition, was accompanied by much smaller persistent Na currents () and distinctive resurgent Na currents (), which were also blocked by TTX. ATX-II, a toxin that slows Na channel inactivation, enhanced in immature and mature calyces. 4,9-Anhydro-TTX (4,9-ah-TTX), which selectively blocks Nav1.6 channels, abolished the enhanced in mature, but not immature, calyces. Therefore, Nav1.6 channels mediate a component of and in mature calyces, but are minimally expressed at early postnatal days. was expressed in less than one-third of calyces at P6-P8, but expression increased with development, and in mature cristae was frequently found in peripheral calyces. served to increase the availability of Na channels following brief membrane depolarizations. In current clamp, the rate and regularity of action potential firing decreased in mature peripheral calyces following 4,9-ah-TTX application. Therefore, Nav1.6 channels are upregulated during development, contribute to , and , and may regulate excitability by enabling higher mean discharge rates in a subpopulation of mature calyx afferents. Action potential firing patterns differ between groups of afferent neurons innervating vestibular epithelia. We investigated the biophysical properties of Na currents in specialized vestibular calyx afferent terminals during postnatal development. Mature calyces express Na currents with transient, persistent, and resurgent components. Nav1.6 channels contribute to resurgent Na currents and may enhance firing in peripheral calyx afferents. Understanding Na channels that contribute to vestibular nerve responses has implications for developing new treatments for vestibular dysfunction.
前庭传入神经元将外周前庭终器中的毛细胞的信息传递到中枢核团。初级前庭传入神经元可以以高频率发射动作电位，传入的发射模式随前庭神经上皮中神经末梢末端的位置而变化。末梢与毛细胞接触，形成小的接触小体或大的杯状末端。为了研究钠离子电流（）在发射机制中的作用，我们研究了带杯状末端的传入纤维中的生物物理特性。在不同的出生后年龄（幼年期[出生后第 5-8 天，年轻期[出生后第 13-15 天]和成熟期[出生后第 30-45 天]）的沙鼠壶腹嵴的薄片中，从杯状末端进行全细胞膜片钳记录。在成熟的杯状末端，300 nM 河豚毒素（TTX）完全阻断大的瞬态钠电流（）。此外，还伴有较小的持续钠电流（）和特征性的复发性钠电流（），这两种电流也被 TTX 阻断。ATX-II 是一种减慢钠通道失活的毒素，增强了幼稚和成熟杯状末端的。4,9-脱水 TTX（4,9-ah-TTX），选择性阻断 Nav1.6 通道，消除了成熟杯状末端增强的，而在幼年期则没有。因此，Nav1.6 通道介导了成熟杯状末端中的成分和，而在出生后早期表达很少。在 P6-P8 时，少于三分之一的杯状末端表达，但随着发育表达增加，在成熟的壶腹嵴中，外周杯状末端经常发现。增加了短暂膜去极化后钠通道的可利用性。在电流钳中，应用 4,9-ah-TTX 后，成熟的外周杯状末端的动作电位发射率和规律性降低。因此，Nav1.6 通道在发育过程中上调，有助于，和，并通过使成熟杯状传入神经纤维亚群的平均放电率更高，从而调节兴奋性。支配前庭上皮的传入神经元群体之间的动作电位发射模式不同。我们研究了出生后发育过程中专门的前庭杯状传入末端的钠离子电流的生物物理特性。成熟的杯状末端表达具有瞬态、持续和复发性成分的钠电流。Nav1.6 通道有助于复发性钠电流，并可能增强外周杯状传入纤维的放电。了解有助于前庭神经反应的钠通道对开发新的前庭功能障碍治疗方法具有重要意义。
