Impact of 4-aminopyridine on vestibulo–ocular reflex performance
Impact of 4-aminopyridine on vestibulo–ocular reflex performance
复制标题
4-氨基吡啶对前庭眼反射性能的影响
DOI：
10.1007/s00415-019-09452-4
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发表时间：
2019
影响因子：
6
通讯作者：
Straka H.
中科院分区：
文献类型：
--
作者：
I Gusti Bagus M;Gordy C;Sanchez-Gonzalez R;Strupp M;Straka H.
前庭-眼反射（VOR）由频率调谐通路介导，所述频率调谐通路分别将头部运动/位置相关的感觉信号的不同动态和静态方面转换成眼外运动命令。电压依赖性钾电导，如由Kv1.1形成的那些对于VOR电路元件编码高度瞬态运动分量的能力是重要的。在这里，我们描述了Kv1.1通道阻滞剂4-氨基吡啶（4-AP）的自发和运动诱发放电的上级斜肌运动神经元的影响。棘波活动记录从运动神经在分离的制剂非洲爪蟾adopole。在静态条件下，1-10 µM 4-AP的浴应用增加了自发放电率，并引起了重复的尖峰脉冲。在运动刺激过程中，4-AP也增加和延迟了峰值放电率，表明这种药物影响前庭诱发的眼球运动的幅度和时间。Kv1.1在这个发育阶段的幼虫Xenopus粗前庭传入纤维中的表达表明，在4-AP存在下，眼外运动输出的改变主要来自于不规则放电前庭传入的放电率增加，其沿着沿着VOR电路传播。在临床和实验室中，观察到的4-AP介导的外周前庭输入在静息和动态条件下的增加可以通过间接增加小脑浦肯野细胞放电来促进观察到的4-AP在下拍和上拍眼球震颤以及发作性共济失调2型中的治疗效果。
Vestibulo–ocular reflexes (VOR) are mediated by frequency-tuned pathways that separately transform the different dynamic and static aspects of head motion/position-related sensory signals into extraocular motor commands. Voltage-dependent potassium conductances such as those formed by Kv1.1 are important for the ability of VOR circuit elements to encode highly transient motion components. Here we describe the impact of the Kv1.1 channel blocker 4-aminopyridine (4-AP) on spontaneous and motion-evoked discharge of superior oblique motoneurons. Spike activity was recorded from the motor nerve in isolated preparations ofXenopus laevistadpoles. Under static conditions, bath application of 1–10 µM 4-AP increased the spontaneous firing rate and provoked repetitive bursts of spikes. During motion stimulation 4-AP also augmented and delayed the peak firing rate suggesting that this drug affects the magnitude and timing of vestibular-evoked eye movements. The exclusive Kv1.1 expression in thick vestibular afferent fibers in larvalXenopusat this developmental stage suggests that the altered extraocular motor output in the presence of 4-AP mainly derives from a firing rate increase of irregular firing vestibular afferents that propagates along the VOR circuitry. Clinically and pharmacologically, the observed 4-AP-mediated increase of peripheral vestibular input under resting and dynamic conditions can contribute to the observed therapeutic effects of 4-AP in downbeat and upbeat nystagmus as well as episodic ataxia type 2, by an indirect increase of cerebellar Purkinje cell discharge.
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影响因子：
6
作者：
Kalla R;Teufel J;Feil K;Muth C;Strupp M
通讯作者：
Strupp M
影响因子：
3.4
作者：
Branoner F;Straka H
通讯作者：
Straka H
影响因子：
5.3
作者：
Carriot, Jerome;Jamali, Mohsen;Cullen, Kathleen E.
通讯作者：
Cullen, Kathleen E.
DOI：
10.1111/j.1749-6632.2011.06149.x
发表时间：
2011-01-01
期刊：
BASIC AND CLINICAL OCULAR MOTOR AND VESTIBULAR RESEARCH
影响因子：
--
作者：
Glasauer, Stefan;Roessert, Christian;Strupp, Michael
通讯作者：
Strupp, Michael
影响因子：
6
作者：
Soupiadou, Parthena;Branoner, Francisco;Straka, Hans
通讯作者：
Straka, Hans