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Journal of Neurology

, Volume 266, Supplement 1, pp 93–100 | Cite as

Impact of 4-aminopyridine on vestibulo–ocular reflex performance

  • Marliawaty I Gusti Bagus
  • Clayton Gordy
  • Rosario Sanchez-Gonzalez
  • Michael Strupp
  • Hans StrakaEmail author
Original Communication
  • 161 Downloads

Abstract

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 of Xenopus laevis tadpoles. 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 larval Xenopus at 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.

Keywords

Vestibulo–ocular reflex Semicircular canal Extraocular motoneurons Potassium channels 

Notes

Acknowledgements

The authors acknowledge financial support from the German Science Foundation (CRC 870; STR 478/3-1; RTG 2175) and the German Federal Ministry of Education and Research under the Grant code 01 EO 0901.

Compliance with ethical standards

Conflicts of interest

The authors declare no competing financial interests.

Ethical standards

All studies have been approved by the appropriate ethics committee (ROB-55.2-2532.Vet_03-17-24) and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department Biology IILudwig-Maximilians-University MunichPlaneggGermany
  2. 2.Graduate School of Systemic NeurosciencesLudwig-Maximilians-University MunichPlaneggGermany
  3. 3.Department of Neurology and German Center for Vertigo and Balance Disorders (DSGZ)Ludwig-Maximilians-UniversityMunichGermany

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