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European Archives of Oto-Rhino-Laryngology

, Volume 272, Issue 10, pp 2703–2711 | Cite as

Decreased calcium-activated potassium channels by hypoxia causes abnormal firing in the spontaneous firing medial vestibular nuclei neurons

  • Hong Xie
  • Yu-qin Zhang
  • Xin-liang Pan
  • Shu-hui WuEmail author
  • Xiang Chen
  • Jie Wang
  • Hua Liu
  • Xiao-zhong Qian
  • Zhi-guo Liu
  • Lie-Ju Liu
Otology

Abstract

Vertebrobasilar insufficiency (VBI) presents complex varied clinical symptoms, including vertigo and hearing loss. Little is known, however, about how Ca2+-activated K+ channel attributes to the medial vestibular nucleus (MVN) neural activity in VBI. To address this issue, we performed whole-cell patch clamp and quantitative polymerase chain reaction (qPCR) to examine the effects of hypoxia on neural activity and the changes of the large conductance Ca2+ activated K+ channels (BKCa channels) in the MVN neurons in brain slices of male C57BL/6 mice. Brief hypoxic stimuli of the brain slices containing MVN were administrated by switching the normoxic artificial cerebrospinal fluid (ACSF) equilibrated with 21 % O2/5 % CO2 to hypoxic ACSF equilibrated with 5 % O2/5 % CO2 (balance N2). 3-min hypoxia caused a depolarization in the resting membrane potential (RM) in 8/11 non-spontaneous firing MVN neurons. 60/72 spontaneous firing MVN neurons showed a dramatic increase in firing frequency and a depolarization in the RM following brief hypoxia. The amplitude of the afterhyperpolarization (AHPA) was significantly decreased in both type A and type B spontaneous firing MVN neurons. Hypoxia-induced firing response was alleviated by pretreatment with NS1619, a selective BKCa activator. Furthermore, brief hypoxia caused a decrease in the amplitude of iberiotoxin-sensitive outward currents and mRNA level of BKCa in MVN neurons. These results suggest that BKCa channels protect against abnormal MVN neuronal activity induced by hypoxia, and might be a key target for treatment of vertigo and hearing loss in VBI.

Keywords

Hypoxia Calcium-activated potassium channels Whole-cell recording Medial vestibular nucleus Slice 

Abbreviations

BKCa

Large conductance calcium-activated potassium channels

VBI

Vertebrobasilar insufficiency

MVN

Medial vestibular nucleus

ACSF

Artificial cerebrospinal fluid

IBTX

Iberiotoxin

Notes

Conflict of interest

The authors declare that they have no competing financial interests.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Hong Xie
    • 1
  • Yu-qin Zhang
    • 2
  • Xin-liang Pan
    • 3
  • Shu-hui Wu
    • 4
    Email author
  • Xiang Chen
    • 4
  • Jie Wang
    • 4
  • Hua Liu
    • 4
  • Xiao-zhong Qian
    • 4
  • Zhi-guo Liu
    • 5
  • Lie-Ju Liu
    • 5
  1. 1.Jingzhou Central HospitalJingzhouPeople’s Republic of China
  2. 2.Department of NeurologyAnhui No.2 Provincial People’s HospitalHefeiPeople’s Republic of China
  3. 3.Department of OtolaryngologyHead and Neck Surgery, Qilu Hospital, Shandong UniversityJinanPeople’s Republic of China
  4. 4.Department of Otolaryngology, Shuguang Hospital Baoshan BranchShanghai University of Traditional Chinese MedicineShanghaiPeople’s Republic of China
  5. 5.Institution of NutritionWuhan Polytechnic UniversityWuhanPeople’s Republic of China

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