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

Abstract
Vertebrobasilar insufficiency (VBI) presents complex varied clinical symptoms, including vertigo and hearing loss. Little is known, however, about how Ca(2+)-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 Ca(2+) 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.
AuthorsHong Xie, Yu-qin Zhang, Xin-liang Pan, Shu-hui Wu, Xiang Chen, Jie Wang, Hua Liu, Xiao-zhong Qian, Zhi-guo Liu, Lie-Ju Liu
JournalEuropean archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery (Eur Arch Otorhinolaryngol) Vol. 272 Issue 10 Pg. 2703-11 (Oct 2015) ISSN: 1434-4726 [Electronic] Germany
PMID25173490 (Publication Type: Journal Article)
Chemical References
  • Potassium Channels, Calcium-Activated
Topics
  • Animals
  • Disease Models, Animal
  • Hypoxia (metabolism, physiopathology)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Potassium Channels, Calcium-Activated (metabolism)
  • Vestibular Diseases (metabolism, physiopathology)
  • Vestibular Nuclei (metabolism, physiopathology)

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